Information on EC 2.7.11.15 - beta-adrenergic-receptor kinase

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The expected taxonomic range for this enzyme is: Coelomata

EC NUMBER
COMMENTARY
2.7.11.15
-
RECOMMENDED NAME
GeneOntology No.
beta-adrenergic-receptor kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + [beta-adrenergic receptor] = ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
mechanism
-
ATP + [beta-adrenergic receptor] = ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
sequential mechanism
-
ATP + [beta-adrenergic receptor] = ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
regulation mechanism
-
ATP + [beta-adrenergic receptor] = ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
substrate and activator binding site structure, active site structure, structure-function relationship, overview
-
ATP + [beta-adrenergic receptor] = ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:[beta-adrenergic receptor] phosphotransferase
Requires G-protein for activation and therefore belongs to the family of G-protein-dependent receptor kinases (GRKs). Acts on the agonist-occupied form of the receptor; also phosphorylates rhodopsin, but more slowly. Does not act on casein or histones. The enzyme is inhibited by Zn2+ and digitonin but is unaffected by cyclic-AMP (cf. EC 2.7.11.14, rhodopsin kinase and EC 2.7.11.16, G-protein-coupled receptor kinase).
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
ark
P25098
-
beta adrenergic receptor kinase
-
-
beta-adrenergic receptor kinase
-
-
-
-
beta-adrenergic receptor kinase
-
-
beta-adrenergic receptor kinase
P21146
-
beta-adrenergic receptor kinase
-
-
beta-adrenergic receptor kinase
-
-
beta-adrenergic receptor kinase 1
P25098
-
beta-adrenergic receptor kinase 1
Q64682
-
beta-adrenergic receptor kinase 1
P26817
-
beta-adrenergic receptor kinase 2
P26818
-
beta-adrenergic receptor kinase 2
P35626
-
beta-adrenergic receptor kinase 2
P26819
-
beta-adrenergic receptor-specific kinase
-
-
-
-
beta-AR kinase
-
-
-
-
beta-ARK
-
-
-
-
beta-ARK
-
-
beta-ARK 1
-
-
-
-
beta-ARK 2
-
-
-
-
beta-receptor kinase
-
-
-
-
betaAR kinase 1
-
-
betaARK
-
-
betaARK
-
-
betaARK1
-
-
betaARK1
-
-
betaARK1
-
-
betaARK1
-
-
betaARK2
-
-
betabeta-adrenergic receptor kinase 1
-
-
carboxyl-terminus of beta-adrenergic receptor kinase
-
-
G protein-coupled receptor kinase
-
-
G protein-coupled receptor kinase
-
-
G protein-coupled receptor kinase 2
-
-
G protein-coupled receptor kinase 2
O97627
-
G protein-coupled receptor kinase 2
-
-
G protein-coupled receptor kinase 2
P32866
-
G protein-coupled receptor kinase 2
-
-
G protein-coupled receptor kinase 2
P25098
-
G protein-coupled receptor kinase 2
-
-
G protein-coupled receptor kinase 2
-
-
G protein-coupled receptor kinase 3
-
-
G protein-coupled receptor kinase 3
-
-
G protein-coupled receptor kinase 3
-
-
G protein-coupled receptor kinase 3
-
-
G protein-coupled receptor kinase-2
-
-
G protein-coupled receptor kinase-2
P26819
-
G protein-coupled receptor kinase-3
-
-
G protein-coupled receptor regulatory kinase
-
-
G protein-coupled receptor regulatory kinase 2
P32866
-
G-protein coupled receptor kinase 2
-
-
G-protein coupled receptor kinase 2
-
-
G-protein coupled receptor kinase 2
Mus musculus C75BL/6
-
-
-
G-protein receptor kinase 2
-
-
G-protein-coupled receptor kinase 2
-
-
G-protein-coupled receptor kinase 2
-
-
G-protein-coupled receptor kinase-2
-
-
GPCR kinase
-
-
GPCR kinase 2
-
-
GRK2
-
-
-
-
GRK2
P25098
-
GRK2
P35626
-
GRK2
-
-
GRK2
Q3UYH7
-
GRK2
Mus musculus C75BL/6
-
;
-
GRK3
-
-
-
-
GRK3
-
-
guanine nucleotide-binding protein-coupled receptor kinase
-
-
kinase (phosphorylating), beta-adrenergic-receptor
-
-
-
-
additional information
-
the enzymes belong to the family of G protein-coupled receptor kinases
additional information
-
enzymes belong to the GRK family, GRK2 and GRK3, i.e. betaARK1 and betaARK2, form the betaARK subfamily
additional information
-
the enzyme belongs to the beta-adrenergic receptor kinase subfamily
additional information
-
the enzyme belongs to the betaARK subfamily of the GRK family
additional information
-
the enzyme belongs to the G-protein-coupled receptor kinase family
additional information
-
the enzyme belongs to the GRK2 subfamily, consisting of GRK2, beta-ARK1, GRK3, and beta-ARK2
additional information
-
the nezyme belongs to the serine/threonine kinase family
additional information
-
the enzyme belongs to the beta-adrenergic receptor kinases subfamily
additional information
-
enzymes belong to the GRK family, GRK2 and GRK3, i.e. betaARK1 and betaARK2, form the betaARK subfamily
additional information
-, P26819
GRK2 and GRK3 constitute a subfamily among the different GRK isoforms
CAS REGISTRY NUMBER
COMMENTARY
102925-39-3
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
2 isozymes betaARK1 and betaARK2; enzyme exists in 2 subtypes: beta-ARK 1 and beta-ARK 2
-
-
Manually annotated by BRENDA team
beta-ARK 1 and 2; enzyme exists in 2 subtypes: beta-ARK 1 and beta-ARK 2
-
-
Manually annotated by BRENDA team
beta-ARK 1; enzyme exists in 2 subtypes: beta-ARK 1 and beta-ARK 2
-
-
Manually annotated by BRENDA team
enzyme exists in 2 subtypes: beta-ARK 1 and beta-ARK 2
-
-
Manually annotated by BRENDA team
enzyme exists in 2 subtypes: beta-ARK 1 and beta-ARK 2; major isoform beta-ARK 1
-
-
Manually annotated by BRENDA team
North American opossum, gene GRK2
SwissProt
Manually annotated by BRENDA team
; beta-ARK 2, enzyme exists in 2 subtypes: beta-ARK1 and 2
SwissProt
Manually annotated by BRENDA team
enzyme exists in 2 subtypes: beta-ARK1 and 2; major isoform beta-ARK 1
-
-
Manually annotated by BRENDA team
major isoform beta-ARK 1
-
-
Manually annotated by BRENDA team
no splicing variants of GRK2
-
-
Manually annotated by BRENDA team
recombinant beta-ARK 1 holoenzyme
-
-
Manually annotated by BRENDA team
Syrian hamster, healthy F1b and cardiomyopathic BIO53.58, 7, 15 and 20 weeks old, beta-ARK 1
-
-
Manually annotated by BRENDA team
beta-ARK 1
-
-
Manually annotated by BRENDA team
beta-ARK 1; transgenic mouse
-
-
Manually annotated by BRENDA team
C56BL/6-CBA hybrid mice; GRK2; C56BL/6-CBA hybrid mice
-
-
Manually annotated by BRENDA team
C57BL/six mice
-
-
Manually annotated by BRENDA team
C75BL/6 mice
-
-
Manually annotated by BRENDA team
healthy and heart-failure rats
-
-
Manually annotated by BRENDA team
Mus musculus C75BL/6
C57BL/six mice
-
-
Manually annotated by BRENDA team
Mus musculus C75BL/6
C75BL/6 mice
-
-
Manually annotated by BRENDA team
; beta-ARK 1, 2 isoenzymes beta-ARK 1 and 2, adult Sprague-Dawley rats
SwissProt
Manually annotated by BRENDA team
; beta-ARK 2, 2 isoenzymes beta-ARK 1 and 2, adult Sprague-Dawley rats
SwissProt
Manually annotated by BRENDA team
beta-ARK 1
-
-
Manually annotated by BRENDA team
beta-ARK 1; male Wistar rats
-
-
Manually annotated by BRENDA team
GRK2; male Wistar rats
SwissProt
Manually annotated by BRENDA team
healthy and heart-failure rats
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
transgenic mice with cardiac-specific overexpression of GRK2 negatively impact cardiac metabolism by inhibiting glucose uptake and desensitization of insulin signaling, which increases after ischemic injury and precedes heart failure development. Mechanistically, GRK2 interacts with and directly phosphorylates insulin receptor substrate-1 (IRS1) in cardiomyocytes causing insulin-dependent negative signaling feedback including inhibition of membrane translocation of the glucose transporter, GLUT4
malfunction
-
using gprk2 mutant flies its shown that G-protein-coupled receptor kinase 2 regulates cAMP-dependent Hedgehog signaling
malfunction
-
the influence of GRK2 levels is investigated in insulin signaling in myoblasts and adipocytes with experimentally increased or silenced levels of GRK2, as well as in GRK2 hemizygous animals expressing 50% lower levels of this kinase in three different models of insulin resistance: TNF-alpha infusion, aging, and high-fat diet (HFD). GRK2 levels are increased by 2fold in muscle and adipose tissue in the animal models tested. In contrast, hemizygous GRK2 mice show enhanced insulin sensitivity and do not develop insulin resistance by TNF-alpha, aging, or high-fat diet. Reduced GRK2 levels induce a lean phenotype and decrease age-related adiposity
malfunction
-
overexpression of GRK2 in normal cardiac fibroblasts recapitulates a heart failure phenotype with minimal inhibition of collagen synthesis following beta-agonist stimulation. Knockdown of GRK2 expression in normal cardiac fibroblasts enhances cAMP production and leads to greater beta-agonist-mediated inhibition of basal and TGF beta-stimulated collagen synthesis versus control. Inhibition of GRK2 activity in failing cardiac fibroblasts by expression of the GRK2 inhibitor, GRK2ct, or siRNA-mediated knockdown restores beta-agonist stimulated inhibition of collagen synthesis and decreases collagen synthesis in response to TGF beta stimulation
malfunction
-
GRK2 kinase activity and, therefore, histamine H2 receptor phosphorylation, is required to achieve H2R internalization but not receptor desensitization
malfunction
-
morpholino silencing of the zebrafish ortholog of Gprk2 in fish embryos causes impaired cytokine expression after Escherichia coli infection
malfunction
-
using a genome-wide RNAi screen Grk2 is identified as a conserved regulator of NF-kappaB signaling
malfunction
-
RNA silencing of GRK5 in HeLa cells impairs NF-kappaB reporter activity
malfunction
-
using siRNA-mediated knockdown of GRK2 in mouse embryonic fibroblasts it is shown that GRK2 is required for efficient propagation of viruses from the Flaviviridae family and that a decrease in GRK2 level alters both virus entry and RNA genome amplification
physiological function
-
GRK2 regulates membrane protrusion and collective migration of a cell sheet during wound closure in MDCK cell monolayers at least partly through phosphorylation of ezrin/radixin/moesin (ERM) proteins, in particular radixin
physiological function
-
insulin signaling is regulated by GRK2 levels in adipocytes and myocytes
physiological function
-
GRK2 plays a significant role in regulating collagen synthesis in adult human cardiac fibroblasts
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
-, the phosphorylase kinase phosphorylates proteins and proteolytic fragments thereof, phosphorylation of multiple residues in the substrate sequence
-
-
?
ATP + alpha-synuclein
ADP + phosphorylated alpha-synuclein
show the reaction diagram
-
colocalization of GRK2, GRK5, alpha-synuclein, and tau in neurodegenerative disorders characterized by fibrillary tau inclusions and/or alpha-synuclein-enriched Lewy bodies, overview, phosphorylation at Ser129
-
-
?
ATP + alpha1 beta-adrenergic receptor
ADP + phosphorylated alpha1 beta-adrenergic receptor
show the reaction diagram
P26819
-, substrate specificities of GRK2 and GRK3 in cardiac myocytes, overview
-
-
?
ATP + alpha1-adrenergic receptor
ADP + alpha1-adrenergic receptor phosphate
show the reaction diagram
P26819
-
-
-
?
ATP + alpha1D-adrenergic receptor
ADP + alpha1D-adrenergic receptor phosphate
show the reaction diagram
-
-, inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances alpha1D-adrenergic receptor constriction and signalling, overview
-
-
?
ATP + alpha2-adrenergic receptor
ADP + phospho-alpha2-adrenergic receptor
show the reaction diagram
-
-
-
-
?
ATP + alpha2-adrenergic receptor
ADP + phospho-alpha2-adrenergic receptor
show the reaction diagram
-
dependent on agonist occupancy by (-)-epinephrine, equally effective as beta-adrenergic receptor, incorporation of 7-8 mol phosphate/mol receptor
-
-
?
ATP + alpha2-adrenergic receptor
ADP + phospho-alpha2-adrenergic receptor
show the reaction diagram
-
agonist-induced phosphorylation
-
-
?
ATP + alpha2-adrenergic receptor
ADP + phospho-alpha2-adrenergic receptor
show the reaction diagram
-
from human platelets
-
-
?
ATP + alpha2A-adrenergic receptor
ADP + phosphorylated alpha2A-adrenergic receptor
show the reaction diagram
-
-, interaction with GRK2 via the second and third intracellular loop of the receptor, determination of regions required for specific interaction and phosphorylation activity utilizing recombinant GST-tagged wild-type and several mutant alpha2A AR substrates, residues R225, R226, R218, K320, R322, and K358 are important, overview
-
-
?
ATP + angiotensin receptor
ADP + phosphorylated angiotensin receptor
show the reaction diagram
-
-, phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
phosphorylation sites
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
phosphorylation sites are located mainly at the C-terminal tail of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
incorporation of 7-8 mol phosphate/mol receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
incorporation of about 9 mol phosphate/mol receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P21146
beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P26817, P26819
beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P21146
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-, Q64682
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P26817, P26819
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P35626
specifically phosphorylates the agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
similar rates of beta-ARK 1 and 2 for beta2-adrenergic receptor phosphorylation
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
human beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
human beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
human beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
human beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
human beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
at a similar rate as muscarinic cholinergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
at a similar rate as alpha2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
substrates: wild-type and mutants of beta2-AR, synergistic action of beta-ARK and cAMP-dependent protein kinase depends on the palmitoylation state of the receptor, putative phosphorylation sites of beta2-AR
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
incorporation of up to 5 mol phosphate/mol receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
incorporation of up to 5 mol phosphate/mol receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-ARK 1, substrate specificity, the overall topological structure of the activated receptor plays a key role in regulating signal-dependent receptor phosphorylation
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P26817, P26819
beta-ARK 1 is more active than beta-ARK 2
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
phosphate is incorporated solely into Ser-residues
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-ARK 2 has a 25% lower specific activity than beta-ARK 1 towards rhodopsin and beta2-AR
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
incorporation of 6-8 mol phosphate/mol receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-AR from Sf9 cells
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-ARK 1: substrate recognition mechanism, consensus sequence required for substrates, 3-dimensional model structure of the catalytic domain, potential phosphorylation sites of human beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-AR from hamster lung
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-AR from hamster lung
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P21146
beta-AR from hamster lung
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-AR from hamster lung
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-AR from hamster lung
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-AR from hamster lung
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-AR from hamster lung
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P26817, P26819
beta-AR from hamster lung
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P21146
beta-AR is a much better substrate than rhodopsin
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-AR is a much better substrate than rhodopsin
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-AR is a much better substrate than rhodopsin
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P26817, P26819
general role in the desensitization of synaptic receptors
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates and inactivates beta-AR after stimulation by receptor agonists, facilitating the binding of the inhibitor protein beta-arrestin to the receptor, during myocardial ischemia the membrane activity of beta-ARK is increased
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-, Q64682
beta-ARK 1 might be involved in uncoupling and down-regulation of beta-AR, presumably both beta1- and beta2-AR, in failing hearts via receptor phosphorylation
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
presumably modulates some receptor-mediated immune functions
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
role of beta-ARK 1 in heart failure, myocardial development and function
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
natural substrate: beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
natural substrate: beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-ARK 1 and 2 may have a similar substrate specificity in vivo
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
regulation of the beta-AR function in vivo
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
plays, together with cAMP-dependent protein kinase, an important role in agonist-promoted receptor desensitization, coordinated regulatory mechanism involving sequential depalmitoylation and phosphorylation of the beta2-AR by the two kinases
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P21146
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P35626
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P21146
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P26817, P26819
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P35626
functional role of the beta-ARK/beta-arrestin mechanism of receptor desensitization in immune cells
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
agonist-activated receptor substrate
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
betaARK is involved in myocardial beta-adrenergic receptor signaling, enzyme dysfunction can cause heart failure, regulation mechanism and physiology, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
betaARK1 is responsible for desensitization and down regulation of beta-adrenergic receptors
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
desensitization of the receptor by GRK2 and GRK3
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis via clathrin-coated pits
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
G-protein-coupled receptor kinase-2 and beta-arrestin-2 are involved in exercise-induced beta-adrenergic receptor trafficking from cytosol to membranes in adipocytes, role in beta-adrenergic receptor-ubiquitination in the ubiquitin-proteasome pathway
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
mouse wild-type receptor, cytosolic phosphorylation domain of the substrate, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
receptor desensitization by phosphorylation
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
GRK3 and GRK2 are involved in down-regulation of the alpha2B-adrenoceptor, regulation of the pathway, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
in human heart failure, impaired beta-adrenergic receptor signaling compromises cardiac sensitivity to inotropic stimulation, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
phosphorylation and internalization of the receptor requires clathrin, GRK2 specifically phosphorylates the activated form of the receptor that promotes the translocation of beta-arrestins to the plasma membrane, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
the enzyme is involved in regulation of the beta-adrenergic receptor signaling by inhibiting arrestin recruitment to the receptor and subsequent desensitization and internalization, regulation of GRK2 by S-nitrosylation, molecular mechanism, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
mapping of S-nitrosylation sites and regulatory locus in GRK2
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
recombinantly expressed beta-adrenergic receptor in U2-OS cells, mapping of S-nitrosylation sites and regulatory locus in GRK2
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
urea-treated rod outer segments as substrate
-
-
?
ATP + beta-adrenergic receptor
ADP + beta-adrenergic receptor phosphate
show the reaction diagram
-
-
-
-
?
ATP + beta-adrenergic receptor
ADP + beta-adrenergic receptor phosphate
show the reaction diagram
-
-
-
-
?
ATP + beta-adrenergic receptor
ADP + beta-adrenergic receptor phosphate
show the reaction diagram
-
the mechanism of myocardial beta-adrenergic receptor desensitization during cardiac surgery involves GRK2, overview
-
-
?
ATP + beta-casein
ADP + phosphorylated beta-casein
show the reaction diagram
-
recombinant HA-tagged wild-type and mutant GRK3
-
-
?
ATP + beta-tubulin
ADP + phosphorylated beta-tubulin
show the reaction diagram
-
purified substrate from porcine brain or human GST-tagged protein recombinantly expressed in Escherichia coli, phosphorylation of betaI- and betaIII-tubulin at Thr409, Ser420, and, in betaIII-tubulin, also at Ser420 of the C-terminal outer surface of the substrate protein
-
-
?
ATP + beta1-adrenergic receptor
ADP + beta1-adrenergic receptor phosphate
show the reaction diagram
P26819
-
-
-
?
ATP + beta2-adrenergic receptor
ADP + phosphorylated beta2-adrenergic receptor
show the reaction diagram
-
-, desensitization of the receptor with subsequent decline in the stimulatory effects of beta2-adrenergic agonists over time, the receptor is involved in alveolar Na+ and water clearance
-
-
?
ATP + beta2-adrenergic receptor
ADP + beta2-adrenergic receptor phosphate
show the reaction diagram
-
-, role of GRK activity in the regulation of beta2 adrenergic signaling, feedback mechanism, overview
-
-
?
ATP + calcium-sensing receptor
ADP + calcium-sensing receptor phosphate
show the reaction diagram
-
GRK2, homologous desensitization of G protein-coupled receptors is generally mediated by GRKs through phosphorylation-dependent and independent mechanisms, GRK2 can phosphorylate calcium-sensing receptor and, along with beta-arrestins, can attenuate calcium-sensing receptor-mediated signaling, mechanism, overview
-
-
?
ATP + corticotropin-releasing factor receptor type 1
ADP + phosphorylated corticotropin-releasing factor receptor type 1
show the reaction diagram
-
-
-
-
?
ATP + corticotropin-releasing factor receptor type 1
ADP + phosphorylated corticotropin-releasing factor receptor type 1
show the reaction diagram
-
i.e. CRFR1, phosphorylation leads to desensitization and downregulation of the receptor
-
-
?
ATP + dopamine D1 receptor
ADP + phosphorylated dopamine D1 receptor
show the reaction diagram
O97627
phosphorylation by GRK2 has a regulatory role as part of the PI3K-PKC-GRK2 cascade, hyperserine phosphorylation by GRK2
-
-
?
ATP + dopamine D3 receptor
ADP + phosphorylated dopamine D3 receptor
show the reaction diagram
-
-, the receptor is activated by GRK2 and GRK3 phosphorylation involving beta-arrestins, GRK-mediated regulation of receptor-filamin complex stability and receptor-G protein signaling potential, GRK2 reduces the dopamine D3 receptor signaling, overview
-
-
?
ATP + DREAM
ADP + phosphorylated DREAM
show the reaction diagram
-
i.e. downstream regulatory element antagonist modulator protein, GRK2 mediates phosphorylation of DREAM/potassium channel interacting protein KChIP3, a multifunctional protein of the neuronal calcium sensor subfamily of Ca2+-binding proteins with specific roles in different cell compartments, regulating membrane trafficking of Kv4.2 potassium channel, phosphorylation of Ser95 affects cell surface localization, but not Kv4 channel tetramerization, overview, i.e. downstream regulatory element antagonist modulator protein, GRK2 phosphorylates Ser95
-
-
?
ATP + epidermal growth factor receptor
ADP + phosphorylated epidermal growth factor receptor
show the reaction diagram
-
-
-
-
?
ATP + epithelial Na+ channel
ADP + phosphorylated epithelial Na+ channel
show the reaction diagram
-
-, channel inactivation
-
-
?
ATP + ezrin
ADP + phosphorylated ezrin
show the reaction diagram
-
-, phosphorylation of ezrin affects the 7TM receptor mediated cytoskeletal reorganization
-
-
?
ATP + ezrin
ADP + phosphorylated ezrin
show the reaction diagram
-
GRK2
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
-
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
-
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
-
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
-
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
desensitization by GRK2 of the ligand-activated receptor
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
desensitization of agonist-activated receptor
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
GRK2 performs desensitization of the ligand-activated receptor by phosphorylation
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
phosphorylation has a regulatory role, regulation of the signal transduction involving GRK2 and beta-arrestin, overview
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
regulation mechanism of GRK2, overview, regulation by phosphorylation at specific sites via distinct specific kinases, overview
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
the GPCRs possess multiple phosphorylation sites for serine/threonine kinases
-
-
?
ATP + insulin receptor substrate 1
ADP + phosphorylated insulin receptor substrate 1
show the reaction diagram
-
role of GRK2 in insulin receptor IR signaling, phosphorylation at Ser307 by GRK2
-
-
?
ATP + insulin receptor substrate-1
ADP + phosphorylated-insulin receptor substrate-1
show the reaction diagram
-
-
-
-
?
ATP + LEESSSSDHAERPPG
?
show the reaction diagram
-
-
-
-
?
ATP + M1 muscarinic acetylcholine receptor
ADP + phosphorylated M1 muscarinic acetylcholine receptor
show the reaction diagram
-
-, phosphorylation-dependent and -independent mechanisms in the regulation of M1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 in hippocampal neurons, GRK2 can inhibit the receptor-dependent signaling via phospholipase C, overview
-
-
?
ATP + micro-opioid receptor
ADP + phosphorylated micro-opioid receptor
show the reaction diagram
-
mutant C221V GRK2 shows slightly higher effect on morphine-induced internalization of the micro-opioid receptor compared to the wild-type GRK2, while the effects of mutants L271G, L273Y, and L336F are reduced, overview
-
-
?
ATP + muscarinic acetylcholine receptor
ADP + phospho-muscarinic acetylcholine receptor
show the reaction diagram
-
agonist-dependent phosphorylation, subtype 2
-
-
?
ATP + muscarinic cholinergic receptor
ADP + phospho-muscarinic cholinergic receptor
show the reaction diagram
-
in vitro as good as beta-adrenergic receptor, phosphorylation depends on the presence of a muscarinic agonist ligand, not merely receptor occupancy, the agonist induces a conformational change, which allows phosphorylation, phosphorylation sites: 70% Ser- and 30% Thr-residues, incorporation of 3-4 mol phosphate/mol receptor
-
-
?
ATP + muscarinic cholinergic receptor
ADP + phospho-muscarinic cholinergic receptor
show the reaction diagram
-
from chick heart
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
show the reaction diagram
-
recombinant HA-tagged wild-type and mutant GRK3
-
-
?
ATP + Nedd4
ADP + phosphorylated Nedd4
show the reaction diagram
-
GRK2 interacts with and phosphorylates the ubiquitin protein ligase Nedd4 preventing the binding to proline-rich motifs present in the C-termini of epithelial Na+ channel subunits and inhibition of the channels, overview, recombinant GST-tagged wild-type Nedd-4, no activity with Nedd-4 mutant T466A, GRK2 interacts with and phosphorylates the ubiquitin protein ligase Nedd4 at multiple sites, mapping of phosphorylation sites, overview
-
-
?
ATP + Nedd4-2
ADP + phosphorylated Nedd4-2
show the reaction diagram
-
GRK2 interacts with and phosphorylates the ubiquitin protein ligase Nedd4-2 preventing the binding to proline-rich motifs present in the C-termini of epithelial Na+ channel subunits and inhibition of the channels, overview, GRK2 interacts with and phosphorylates the ubiquitin protein ligase Nedd4-2 at multiple sites, mapping of phosphorylation sites, overview
-
-
?
ATP + p38 MAP kinase
ADP + phosphorylated p38 MAP kinase
show the reaction diagram
-
GRK2 inactivates and regulates MAP kinase p38 modulating p38-dependent physiological processes, p38 and GRK2 are localized in a multimolecular complex, phosphorylation at Thr123 located in the docking groove
-
-
?
ATP + p38 MAP kinase
ADP + phosphorylated p38 MAP kinase
show the reaction diagram
Mus musculus C75BL/6
-
GRK2 inactivates and regulates MAP kinase p38 modulating p38-dependent physiological processes, p38 and GRK2 are localized in a multimolecular complex, phosphorylation at Thr123 located in the docking groove
-
-
?
ATP + PDEgamma
ADP + phosphorylated PDEgamma
show the reaction diagram
-
-, phosphorylation of PDEgamma possibly stimulates EGFR-mediated ERK activation
-
-
?
ATP + PDGFRbeta
ADP + phosphorylated PDGFRbeta
show the reaction diagram
-
-
-
-
?
ATP + peptide
ADP + phosphopeptide
show the reaction diagram
-
beta-ARK 1 and 2 prefer peptide substrates with acidic amino acids N-terminal to a Ser-residue
-
-
?
ATP + peptide
ADP + phosphopeptide
show the reaction diagram
-
beta-ARK 1 prefers peptides containing acidic residues on the N-terminal side of a serine or threonine, presence of activated receptor enhances peptide phosphorylation
-
-
?
ATP + peptide
ADP + phosphopeptide
show the reaction diagram
-
e.g. Leu-Glu-Glu-Ser-Ser-Ser-Ser-Asp-His-Ala-Glu-Arg-Pro-Pro-Gly or Arg-Arg-Arg-Glu-Glu-Glu-Glu-Glu-Ser-Ala-Ala-Ala, role of acidic amino acids in peptide substrates, preference for negatively charged amino acids localized to the N-terminal side of a Ser- or Thr-residue, Ser-containing peptides are 4fold better than Thr-containing, synthetic
-
-
?
ATP + peptide
ADP + phosphopeptide
show the reaction diagram
-
synthetic
-
-
?
ATP + phosducin
ADP + phosphorylated phosducin
show the reaction diagram
-
-
-
-
?
ATP + phosducin
ADP + phosphorylated phosducin
show the reaction diagram
-
phosducin is activated to inhibit Gbetagamma protein
-
-
?
ATP + phosducin
ADP + phosphorylated phosducin
show the reaction diagram
-
GRK2
-
-
?
ATP + platelet-activating factor receptor
ADP + phospho-platelet-activating factor receptor
show the reaction diagram
-
PAF receptor acts as substrate
-
-
?
ATP + platelet-derived growth factor receptor-beta
ADP + phosphorylated platelet-derived growth factor receptor-beta
show the reaction diagram
-
feedback inhibition mechanism, overview, active with the wild-type and mutant Y740F/Y751F PDGFRbeta, GRK2 phosphorylation desensitizes the PDGF receptor-beta, feedback inhibition mechanism, overview
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
-
specifically phosphorylates the agonist-occupied forms of the beta 2-adrenergic receptor and related G protein-coupled receptors
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
P25098
the enzyme mediates agonist-dependent phosphorylation of the beta 2-adrenergic and related G protein-coupled receptors
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
P26818
specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors
-
-
?
ATP + protein
ATP + phosphoprotein
show the reaction diagram
-
specifically phosphorylates the agonist-occupied forms of the beta 2-adrenergic receptor and related G protein-coupled receptors
-
-
?
ATP + protein
ATP + phosphoprotein
show the reaction diagram
P25098
the enzyme mediates agonist-dependent phosphorylation of the beta 2-adrenergic and related G protein-coupled receptors
-
-
?
ATP + protein
ATP + phosphoprotein
show the reaction diagram
P26818
specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors
-
-
?
ATP + protein M33
ADP + phosphorylated protein M33
show the reaction diagram
-
GRK2 is a potent regulator of the mouse cytomegalovirus GPCR protein M33-induced Gq/11 signaling through its ability to phosphorylate M33 and sequester Galphaq/11 proteins dependent on an intact RH domain, the protein M33 is able to induce inositol phosphate accumulation, activate NF-kappaB, and promote smooth muscle cell migration, viral GPCRs like M33 play a role in viral dissemination in vivo, M33 is required for efficient murine cytomegalovirus replication in the mouse, and induces several signlaing pathways, overview, recombinant FLAG-tagged M33 expressed in HEK-293T cells
-
-
?
ATP + R-smad
ADP + phosphorylated R-smad
show the reaction diagram
-
GRK2
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
-
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
-
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
P26819
-
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
-
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
-
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
light-activated rhodopsin
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
light-activated rhodopsin
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
dark-adapted and light-activated rhodopsin in urea-washed rod outer segment membranes
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
light-activated rhodopsin, both isozymes ARK1 and ARK2 prefer acidic amino acids N-terminal to a serine for phosphorylation
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
P26819
substrate in dark-adapted, urea-stripped rod outer segment membranes
-
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
beta-ARK 2 has a 25% lower specific activity than beta-ARK 1 towards rhodopsin and beta2-AR
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
P21146
beta-AR is a much better substrate than rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
beta-AR is a much better substrate than rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
beta-AR is a much better substrate than rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
beta-AR is a much better substrate than rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
P21146
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
light-dependent, actual substrate: light-bleached rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
incorporation of 0.15 mol phosphate/mol rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
incorporation of 0.15 mol phosphate/mol rhodopsin
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
P21146
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
P35626
in form of bovine rod outer segments
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
-
metarhodopsin II, poor substrate
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
P35626
recombinant beta-ARK 2: 40% of efficiency of beta-ARK 1 in phosphorylating rhodopsin
-
?
ATP + rhodopsin
ADP + rhodopsin phosphate
show the reaction diagram
-
cf. EC 2.7.11.14, rhodopsin is also a substrate of GRK2
-
-
?
ATP + ribosomal protein P2
ADP + phosphorylated ribosomal protein P2
show the reaction diagram
-
-, activation of P2
-
-
?
ATP + ribosomal protein P2
ADP + phosphorylated ribosomal protein P2
show the reaction diagram
-
GRK2
-
-
?
ATP + RRRAEAAASAAA
ADP + RRRAEAAApSAAA
show the reaction diagram
-
-
-
-
?
ATP + RRRAEASAA
ADP + RRRAEApSAA
show the reaction diagram
-
poor peptide substrate
-
-
?
ATP + RRRASAAASAA
?
show the reaction diagram
-
poor peptide substrate
-
-
?
ATP + RRRASASAA
?
show the reaction diagram
-
poor peptide substrate
-
-
?
ATP + RRRASpAAASAA
ADP + RRRASpAAASpAA
show the reaction diagram
-
poor peptide substrate, higher catalytic efficiency than RRRASAAASAA
-
-
?
ATP + RRRASpASAA
?
show the reaction diagram
-
poor peptide substrate
-
-
?
ATP + RRREEEEESAAA
?
show the reaction diagram
-
-
-
-
?
ATP + RRREEEEESAAA
?
show the reaction diagram
-
-
-
-
?
ATP + RRREEEEESAAA
?
show the reaction diagram
-
nonreceptor peptide substrate
-
-
?
ATP + RRREEEEESAAA
?
show the reaction diagram
-
good peptide substrate, but the activated receptor is a much better substrate
-
-
?
ATP + Smo
ADP + phosphorylated Smo
show the reaction diagram
-
-, GPRK2 participates in Hedgehog signaling in Drosophila melanogaster, and plays a key role in the Smo signal transduction pathway, when Gprk2 levels are lowered, Smo still accumulates at the cell membrane, but its activation is reduced, overview
-
-
?
ATP + Smoothened protein
ADP + phosphorylated Smoothened
show the reaction diagram
-
GRK2 promotes smoothened signal transduction involved in regulation of cellular proliferation and differentiation through activation of the transcription factor Gli, overview
-
-
?
ATP + Smoothened protein
ADP + phopshorylated Smoothened
show the reaction diagram
-
a seven-transmembrane signaling protein
-
-
?
ATP + synuclein
ADP + phosphorylated synuclein
show the reaction diagram
-
-
-
-
?
ATP + synuclein
ADP + phosphorylated synuclein
show the reaction diagram
-
GRK2
-
-
?
ATP + tubulin
ADP + phosphorylated tubulin
show the reaction diagram
-
-
-
-
?
ATP + tubulin
ADP + phosphorylated tubulin
show the reaction diagram
-
-
-
-
?
ATP + tubulin
ADP + phosphorylated tubulin
show the reaction diagram
-
GRK2
-
-
?
ATP + [beta2-adrenergic receptor]
ADP + [beta2-adrenergic receptor] phosphate
show the reaction diagram
-
-, recombinant FLAG-tagged beta2-adrenergic receptor stably expressed in HEK-293 cells
-
-
?
ATP + [TSH receptor]
ADP + [TSH receptor]phosphate
show the reaction diagram
-
GRK2 and GRK3, receptor activation, GRK2 and GRK3
-
-
?
ezrin + ATP
phosphorylated ezrin + ADP
show the reaction diagram
-
-
-
-
?
GTP + beta-adrenergic receptor
GDP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of beta-AR from hamster lung, GTP can substitute ATP, 2% as effective as ATP
-
?
histamine H2 receptor + ATP
phosphorylated histamine H2 receptor + ADP
show the reaction diagram
-
-
-
-
?
radixin + ATP
phosphorylated radixin + ADP
show the reaction diagram
-
-
-
-
?
tubulin + ATP
phosphorylated-tubulin + ADP
show the reaction diagram
-
-
-
-
?
moesin + ATP
phosphorylated moesin + ADP
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
domain structure
-
-
-
additional information
?
-
-
domain structure
-
-
-
additional information
?
-
-
domain structure
-
-
-
additional information
?
-
P21146
domain structure
-
-
-
additional information
?
-
-
beta-ARK interacts rapidly with a high affinity binding site present in salt-stripped rat liver microsomal membranes, modulation of binding of enzyme
-
-
-
additional information
?
-
-
mechanism and significance of the PH-domain function
-
-
-
additional information
?
-
-
phosphorylates G protein coupled receptors in an agonist-dependent manner
-
-
-
additional information
?
-
-
role of the PH domain, ligand binding characteristics of the PH domain, distinct role for each ligand, i.e. betagamma subunits of G proteins and phosphatidylinositol 4,5-bisphosphate, in enzyme-mediated receptor phosphorylation
-
-
-
additional information
?
-
-
beta-ARK 1 phosphorylates beta2-AR and other G protein-coupled receptors, substrate recognition mechanism, consensus sequence required for substrates, 3-dimensional model structure of the catalytic domain, residues 188-436
-
-
-
additional information
?
-
-
not: alpha1-adrenergic receptor
-
-
-
additional information
?
-
-
not: casein, histones
-
-
-
additional information
?
-
-
rhodopsin kinase, EC 2.7.11.14, is also capable of beta-adrenergic receptor phosphorylation
-
-
-
additional information
?
-
-
very poor substrates: casein, phosvitin
-
-
-
additional information
?
-
P21146
enzyme is important in mediating rapid agonist-specific desensitization
-
-
-
additional information
?
-
-
role for beta ARK in modulating some receptor-mediated immune functions
-
-
-
additional information
?
-
P26817, P26819
general role in the desensitization of synaptic receptors
-
-
-
additional information
?
-
-
Gprk2 is required for egg morphogenesis
-
-
-
additional information
?
-
-
beta-ARK is probably a general adenylate cyclase-coupled receptor kinase
-
-
-
additional information
?
-
-
beta-ARK 1 is a key regulatory enzyme involved in the regulation of G protein-coupled receptors which associate with microsomal and plasma membranes
-
-
-
additional information
?
-
-
plays a pivotal role in phosphorylating and desensitizing G protein-coupled receptors by vitue of pleckstrin homology domain-mediated membrane translocation
-
-
-
additional information
?
-
-
beta-ARK activity is regulated by endogenous G proteins in different intracellular locations
-
-
-
additional information
?
-
-
phosphorylates and regulates receptors coupled to either stimulation or inhibition of adenylate cyclase
-
-
-
additional information
?
-
P26817, P26819
general function in desensitizing of many G protein-coupled receptor systems
-
-
-
additional information
?
-
-
involved in the regulation of G protein-coupled receptor function, beta-ARK 1 appears to be the predominant GRK in early embryogenesis and plays a fundamental role in cardiac development, enzyme participates in intracellular signal transduction mechanisms, which regulate cardiogenesis
-
-
-
additional information
?
-
-
adenovirus-mediated overexpression of phosphoinositide 3-kinase restore contractile function of cardiac myocytes isolated from failing hearts, the recombinant PIK replaces the endogenous PIK in the transgenic pigs, the endogenous PIK shows abnormally increased activity in complex with betaARK1, overview
-
-
-
additional information
?
-
-
betaARK enhances the contractility in heart myocardium via inhibition of Gbetagamma subunits
-
-
-
additional information
?
-
-
betaARK1 binds phosphoinositide 3-kinase, which is by this way targeted to agonist-stimulated beta-adrenergic receptors, where it regulates endocytosis, disruption of the betaARK1-PIK complex leads to restoration of beta-adrenergic receptor signaling and contractile function in heart failure, overview
-
-
-
additional information
?
-
-
betaARK1 inhibition improves beta-adrenergic signaling and contractile function in failing human myocytes
-
-
-
additional information
?
-
-
brain death induction, as well as sham-operation of pigs, lead to uncoupling of the beta-adrenergic receptor with acutely increased myocardial beta-adrenergic receptor kinase activity leading to left ventricular dysfunction
-
-
-
additional information
?
-
-
dopamine D3 receptor binds to G proteins, the coupling is regulated by the filamin expression level
-
-
-
additional information
?
-
-
G protein-coupled receptors are involved in the regulation of diverse physiological processes, mechanisms of G protein-coupled receptor desensitization, e.g. by phosphorylation or feedback inhibition, overview
-
-
-
additional information
?
-
-
GRK2 and GRK3 are involved in methacholine-stimulated inositol 3-phosphate production
-
-
-
additional information
?
-
-
GRK2 expression plays a role in the fly development, GRK2 expression is required in the germline for proper formation of the anterior egg structures, egg hatching, and for early and late embryogenesis
-
-
-
additional information
?
-
-
GRK2 is involved in A2 adenosine receptor response to agonists
-
-
-
additional information
?
-
-
GRK2 mediates endothelin-1-induced insulin resistance via the inhibition of both Galphaq/11 and insulin receptor substrate-1 pathways in 3T3-L1 adipocytes, GRK2 does not affect insulin receptor tyrosine phosphorylation
-
-
-
additional information
?
-
-
GRK2 regulation mechanism of ERK activation involving interaction with mitogen-activated protein kinase, GRK2 diminishes the level of activating phosphorylation of ERK by CCL2 binding to chemokine receptor CCR2 in endothelial cells
-
-
-
additional information
?
-
-
GRK3 is essential for induction of germinal vesicle breakdown, GRK3 forms a complex with beta-arrestin-2 causing G protein-coupled receptor desensitization
-
-
-
additional information
?
-
-
GRKs are involved in diverse physiological processes and pathologies, overview
-
-
-
additional information
?
-
-
phosphorylation of heptahelical receptors by GRK2 is a universal regulatory mehanism leading to desensitization of G protein signaling and to the activation of alternative signaling pathways
-
-
-
additional information
?
-
-
the enzyme is involved in G protein-coupled receptor signal transduction pathways and desensitization, GRK2 is a multiple domain kinase regulating by multiple mechanisms, overview
-
-
-
additional information
?
-
-
betaARK1 interacts with recombinant phosphoinositide 3-kinase expressed in transgenic mice
-
-
-
additional information
?
-
-
GRK2 functionally ineracts with clathrin, phosphoinositol 3-phosphate kinase-gamma, and G protein-coupled receptor kinase interacting protein, GIT
-
-
-
additional information
?
-
-
GRK2 functionally ineracts with clathrin, phosphoinositol 3-phosphate kinase-gamma, and GIT
-
-
-
additional information
?
-
-
GRK2 interacts by direct binding with Galphaq/11, phosphorylation of agonist-activated seven-transmembrane receptors by GRK2
-
-
-
additional information
?
-
-
GRK2 interacts with calmodulin, substrate specificity, GRK2 phosphorylates serine and threonine residues with preceeding acidic amino acid residues
-
-
-
additional information
?
-
-
GRK2 prefers acidic protein sequences for phosphorylation
-
-
-
additional information
?
-
-
peptide phosphorylation study
-
-
-
additional information
?
-
-
substrate specificity, the enzyme depends on basic residues for substrate recognition, the residues at the substrate phosphorylation site greatly influence the enzyme activity, autoregulation by a pseudosubstrate mechanism, overview
-
-
-
additional information
?
-
-
the enzyme contains regulatory sites for Ca2+/calmodulin, protein kinase C, and clathrin
-
-
-
additional information
?
-
-
the GRKs are specific for GPCRs and arrestins, overview
-
-
-
additional information
?
-
-
the M3 muscarinic acetylcholine receptor is no substrate for GRK2 and GRK3
-
-
-
additional information
?
-
-
adrenal GRK2 upregulation mediates sympathetic overdrive in heart failure, adrenal gland-specific GRK2 inhibition reverses alpha2 beta-adrenergic receptor dysregulation in heart failure, resulting in lowered plasma catecholamine levels, improved cardiac beta-adrenergic signaling and function, and increased sympatholytic efficacy of a alpha2 beta-adrenergic agonist
-
-
-
additional information
?
-
-
GPCR-dependent kinases play a major role in agonist-induced phosphorylation and desensitization of G-protein coupled receptors, GRK2 is a component of neuronal and glial fibrillary tau deposits with no preference in tau isoform binding, GRK2 may play a role in hyperphosphorylation of tau in tauopathies
-
-
-
additional information
?
-
-
GRK activity is regulated by phosphorylation through several kinases and by interactions with several cellular proteins, e.g. calmodulin, caveolin or RKIP, GRK also interacts with PI3K, Akt, GIT or MEK, the interactions occur at the RH and PH domains, overview, the GRK interactome: role of GRKs in GPCR regulation and signaling, detailed overview
-
-
-
additional information
?
-
-
GRK-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling and desensitization, beta-arrestin-mediated receptor internalization, activity of GRKs and subcellular targeting is tightly regulated by interaction with receptor domains, G protein subunits, lipids, anchoring proteins and calcium-sensitive proteins, selective binding of activated Galphaq and Galpha-11 to RH domains of GRK2 and GRK3 selectively inhibits Gq signaling
-
-
-
additional information
?
-
-
GRK2 activity leads to translocation of parts of beta-adrenergic receptors to endocytic vesicles
-
-
-
additional information
?
-
-
GRK2 interacts with multiple signaling proteins and is involved in several cellular processes, e.g. expression and regulation of key cardiac seven-transmembrane receptors, 7TM receptors, such as the beta-adrenergic and angiotensin receptors, GRK2 interacts with NCS-1, mechanism, overview, GRK2 inhibition can ameliorate heart failure, molecular mechanism of GRK2 activity regulation, GRK2 is probably involved in regulation of hypertension, overview
-
-
-
additional information
?
-
-
GRK2 is essential, and GRK2-deficient mice are embryonically lethal
-
-
-
additional information
?
-
-
GRK2 negatively regulates glycogen synthesis in mouse liver FL83B cells, regulates basal and insulin-stimulated glycogen synthesis via a post-IR signaling mechanism, and GRK2 may contribute to reduced IR expression and function during chronic insulin exposure
-
-
-
additional information
?
-
-
GRK2 plays a role in sodium transport regulation and is involved in the development of essential hypertension, overview
-
-
-
additional information
?
-
-
GRK2 regulates 7TM G-protein-coupled receptor activity, GRK2 promotes the association between active Smoothened and beta-arrestin 2, overview
-
-
-
additional information
?
-
O97627
insulin-mediated dopamine D1 receptor desensitization and underlying molecular mechanism in opossum kidney cells, overview
-
-
-
additional information
?
-
-
GRK2 and tau do not crossreact
-
-
-
additional information
?
-
-
GRK2 binds to and inhibits Galphaq protein via its N-terminal RGS domain, GRK2 interacts with NCS-1
-
-
-
additional information
?
-
-
GRK2 interacts with a component of the MAPK pathway, as well as with the PI-3K substrate AKT, GRK2 and GRK3 bind the Gbetagamma subunit complex, a process that induces activation of the GRKs
-
-
-
additional information
?
-
-
G protein-coupled receptor kinases and arrestins are key participants in the canonical pathways leading to phosphorylation-dependent G protein-coupled receptor, GPCR, desensitization, endocytosis, intracellular trafficking and resensitization as well as in the modulation of important intracellular signaling cascades by GPCR, structure-function relationships, overview. GRK activity is tightly modulated by mechanisms including phosphorylation by different kinases and interaction with several cellular proteins such as calmodulin, caveolin or RKIP. Different mechanisms of signalling pathways modulation by GRK2, and regulation of GRK2, overview
-
-
-
additional information
?
-
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
-
additional information
?
-
-
Gprk2, a Drosophila member of the G protein-coupled receptor kinases, plays a key role in the Smo, i.e. Smoothened, signal transduction pathway, overview. When Gprk2 levels are lowered, Smo still accumulates at the cell membrane, but its activation is reduced. Regulation of Gprk2 expression by Hh signaling in the wing disc, but Gprk2 is also required for Hh signaling in the wing disc, overview
-
-
-
additional information
?
-
-
GRK-mediated desensitization of beta2-adrenergic receptors is sufficient to cause declines in cAMP signals. GRK-mediated desensitization is primarily responsible for a sustained suppression of beta2AR signaling, overview
-
-
-
additional information
?
-
P26819
GRK2 causes enhanced catecholamine secretion by desensitizing sympatho-inhibitory alpha2-adrenergic receptors of chromaffin cells and thereby aggravating heart failure
-
-
-
additional information
?
-
-
GRK2 in cardiac myocytes catalyzes phosphorylation and desensitization of different G protein-coupled receptors through specificity controlled by their carboxyl-terminal pleckstrin homology domain, overview
-
-
-
additional information
?
-
Q3UYH7
GRK2 is important for myocardial regulation, and is up-regulated in the dysfunctional heart
-
-
-
additional information
?
-
P26819
GRK2 substrate specificity in adult rat cardiac myocytes, overview. GRK2 completely lacks the capacity to attenuate phenylephrine-stimulated IP generation
-
-
-
additional information
?
-
-
GRK3 in cardiac myocytes catalyzes phosphorylation and desensitization of different G protein-coupled receptors through specificity controlled by its carboxyl-terminal pleckstrin homology domain. GRK3 controls cardiac alpha1-adrenergic receptor responsiveness, distinct functions of GRK3 in regulation of cardiac contractility and growth, overview
-
-
-
additional information
?
-
P26819
GRK3 substrate specificity in adult rat cardiac myocytes, overview
-
-
-
additional information
?
-
-
GRK2 also phosphorylates rhodopsin, cf. EC 2.7.11.14
-
-
-
additional information
?
-
-
GRK2 can also phosphorylate non-receptor substrates such as phosducins, synucleins, tubulin, ribosomal protein P2, ezrin, and receptor regulated Smads. The RH domain of GRK2 specifically interacts with Galphaq family members, although it does not stimulate the GTPase activity of Galphaq as efficiently as other classical RGS proteins do, interaction with other oroteins, detailed overview
-
-
-
additional information
?
-
-
GRK2 is also active with rhodopsin, cf. EC 2.7.11.14
-
-
-
additional information
?
-
P26819
GRK2 substrate specificity, overview. GRK2 also shows activity with rhodopsin as substrate, cf. EC 2.7.11.14, GRK3 substrate specificity, overview. GRK3 also shows activity with rhodopsin as substrate, cf. EC 2.7.11.14
-
-
-
additional information
?
-
Q3UYH7
no activity of GRK2 with alpha1-adrenergic receptor. GRK2 does not show class II histone deacetylase kinase activity or interaction with histone deacetylase kinases in vivo
-
-
-
additional information
?
-
-
carboxyl-terminus of GRK2 interacts with Hsp90. Reactive oxygen species (ROS)-mediated mitochrondrial localisation of GRK2 is dependent on Hsp90 binding
-
-
-
additional information
?
-
-
Gprk2 interacts with the Drosophila IkB homolog Cactus
-
-
-
additional information
?
-
-
GRK2 interacts with Hsp90. Reactive oxygen species (ROS)-mediated mitochrondrial localisation of GRK2 is dependent on Hsp90 binding
-
-
-
additional information
?
-
Mus musculus C75BL/6
-
GRK2 is essential, and GRK2-deficient mice are embryonically lethal
-
-
-
additional information
?
-
Mus musculus C75BL/6
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
-
-
-
?
ATP + alpha-synuclein
ADP + phosphorylated alpha-synuclein
show the reaction diagram
-
colocalization of GRK2, GRK5, alpha-synuclein, and tau in neurodegenerative disorders characterized by fibrillary tau inclusions and/or alpha-synuclein-enriched Lewy bodies, overview
-
-
?
ATP + alpha1 beta-adrenergic receptor
ADP + phosphorylated alpha1 beta-adrenergic receptor
show the reaction diagram
P26819
substrate specificities of GRK2 and GRK3 in cardiac myocytes, overview
-
-
?
ATP + alpha1-adrenergic receptor
ADP + alpha1-adrenergic receptor phosphate
show the reaction diagram
P26819
-
-
-
?
ATP + alpha1D-adrenergic receptor
ADP + alpha1D-adrenergic receptor phosphate
show the reaction diagram
-
inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances alpha1D-adrenergic receptor constriction and signalling, overview
-
-
?
ATP + alpha2A-adrenergic receptor
ADP + phosphorylated alpha2A-adrenergic receptor
show the reaction diagram
-
-
-
-
?
ATP + angiotensin receptor
ADP + phosphorylated angiotensin receptor
show the reaction diagram
-
phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P26817, P26819
general role in the desensitization of synaptic receptors
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
specifically phosphorylates and inactivates beta-AR after stimulation by receptor agonists, facilitating the binding of the inhibitor protein beta-arrestin to the receptor, during myocardial ischemia the membrane activity of beta-ARK is increased
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-, Q64682
beta-ARK 1 might be involved in uncoupling and down-regulation of beta-AR, presumably both beta1- and beta2-AR, in failing hearts via receptor phosphorylation
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
presumably modulates some receptor-mediated immune functions
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
role of beta-ARK 1 in heart failure, myocardial development and function
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
natural substrate: beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
natural substrate: beta2-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
beta-ARK 1 and 2 may have a similar substrate specificity in vivo
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
regulation of the beta-AR function in vivo
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
plays, together with cAMP-dependent protein kinase, an important role in agonist-promoted receptor desensitization, coordinated regulatory mechanism involving sequential depalmitoylation and phosphorylation of the beta2-AR by the two kinases
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P21146
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P35626
agonist-occupied form of the receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P21146
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
-
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P26817, P26819
involved in homologous desensitization of beta-adrenergic receptor
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
P35626
functional role of the beta-ARK/beta-arrestin mechanism of receptor desensitization in immune cells
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
agonist-activated receptor substrate
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
betaARK is involved in myocardial beta-adrenergic receptor signaling, enzyme dysfunction can cause heart failure, regulation mechanism and physiology, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
betaARK1 is responsible for desensitization and down regulation of beta-adrenergic receptors
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
desensitization of the receptor by GRK2 and GRK3
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis via clathrin-coated pits
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
G-protein-coupled receptor kinase-2 and beta-arrestin-2 are involved in exercise-induced beta-adrenergic receptor trafficking from cytosol to membranes in adipocytes, role in beta-adrenergic receptor-ubiquitination in the ubiquitin-proteasome pathway
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
GRK3 and GRK2 are involved in down-regulation of the alpha2B-adrenoceptor, regulation of the pathway, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
in human heart failure, impaired beta-adrenergic receptor signaling compromises cardiac sensitivity to inotropic stimulation, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
phosphorylation and internalization of the receptor requires clathrin, GRK2 specifically phosphorylates the activated form of the receptor that promotes the translocation of beta-arrestins to the plasma membrane, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
the enzyme is involved in regulation of the beta-adrenergic receptor signaling by inhibiting arrestin recruitment to the receptor and subsequent desensitization and internalization, regulation of GRK2 by S-nitrosylation, molecular mechanism, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + beta-adrenergic receptor phosphate
show the reaction diagram
-
-
-
-
?
ATP + beta-adrenergic receptor
ADP + beta-adrenergic receptor phosphate
show the reaction diagram
-
the mechanism of myocardial beta-adrenergic receptor desensitization during cardiac surgery involves GRK2, overview
-
-
?
ATP + beta1-adrenergic receptor
ADP + beta1-adrenergic receptor phosphate
show the reaction diagram
P26819
-
-
-
?
ATP + beta2-adrenergic receptor
ADP + phosphorylated beta2-adrenergic receptor
show the reaction diagram
-
desensitization of the receptor with subsequent decline in the stimulatory effects of beta2-adrenergic agonists over time, the receptor is involved in alveolar Na+ and water clearance
-
-
?
ATP + beta2-adrenergic receptor
ADP + beta2-adrenergic receptor phosphate
show the reaction diagram
-
role of GRK activity in the regulation of beta2 adrenergic signaling, feedback mechanism, overview
-
-
?
ATP + calcium-sensing receptor
ADP + calcium-sensing receptor phosphate
show the reaction diagram
-
homologous desensitization of G protein-coupled receptors is generally mediated by GRKs through phosphorylation-dependent and independent mechanisms, GRK2 can phosphorylate calcium-sensing receptor and, along with beta-arrestins, can attenuate calcium-sensing receptor-mediated signaling, mechanism, overview
-
-
?
ATP + corticotropin-releasing factor receptor type 1
ADP + phosphorylated corticotropin-releasing factor receptor type 1
show the reaction diagram
-
i.e. CRFR1, phosphorylation leads to desensitization and downregulation of the receptor
-
-
?
ATP + dopamine D1 receptor
ADP + phosphorylated dopamine D1 receptor
show the reaction diagram
O97627
phosphorylation by GRK2 has a regulatory role as part of the PI3K-PKC-GRK2 cascade
-
-
?
ATP + dopamine D3 receptor
ADP + phosphorylated dopamine D3 receptor
show the reaction diagram
-
the receptor is activated by GRK2 and GRK3 phosphorylation involving beta-arrestins, GRK-mediated regulation of receptor-filamin complex stability and receptor-G protein signaling potential, GRK2 reduces the dopamine D3 receptor signaling, overview
-
-
?
ATP + DREAM
ADP + phosphorylated DREAM
show the reaction diagram
-
i.e. downstream regulatory element antagonist modulator protein, GRK2 mediates phosphorylation of DREAM/potassium channel interacting protein KChIP3, a multifunctional protein of the neuronal calcium sensor subfamily of Ca2+-binding proteins with specific roles in different cell compartments, regulating membrane trafficking of Kv4.2 potassium channel, phosphorylation of Ser95 affects cell surface localization, but not Kv4 channel tetramerization, overview
-
-
?
ATP + epithelial Na+ channel
ADP + phosphorylated epithelial Na+ channel
show the reaction diagram
-
channel inactivation
-
-
?
ATP + ezrin
ADP + phosphorylated ezrin
show the reaction diagram
-
phosphorylation of ezrin affects the 7TM receptor mediated cytoskeletal reorganization
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
-
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
-
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
desensitization by GRK2 of the ligand-activated receptor
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
desensitization of agonist-activated receptor
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
GRK2 performs desensitization of the ligand-activated receptor by phosphorylation
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
phosphorylation has a regulatory role, regulation of the signal transduction involving GRK2 and beta-arrestin, overview
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
regulation mechanism of GRK2, overview, regulation by phosphorylation at specific sites via distinct specific kinases, overview
-
-
?
ATP + insulin receptor substrate 1
ADP + phosphorylated insulin receptor substrate 1
show the reaction diagram
-
role of GRK2 in insulin receptor IR signaling
-
-
?
ATP + insulin receptor substrate-1
ADP + phosphorylated-insulin receptor substrate-1
show the reaction diagram
-
-
-
-
?
ATP + M1 muscarinic acetylcholine receptor
ADP + phosphorylated M1 muscarinic acetylcholine receptor
show the reaction diagram
-
phosphorylation-dependent and -independent mechanisms in the regulation of M1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 in hippocampal neurons, GRK2 can inhibit the receptor-dependent signaling via phospholipase C, overview
-
-
?
ATP + Nedd4
ADP + phosphorylated Nedd4
show the reaction diagram
-
GRK2 interacts with and phosphorylates the ubiquitin protein ligase Nedd4 preventing the binding to proline-rich motifs present in the C-termini of epithelial Na+ channel subunits and inhibition of the channels, overview
-
-
?
ATP + Nedd4-2
ADP + phosphorylated Nedd4-2
show the reaction diagram
-
GRK2 interacts with and phosphorylates the ubiquitin protein ligase Nedd4-2 preventing the binding to proline-rich motifs present in the C-termini of epithelial Na+ channel subunits and inhibition of the channels, overview
-
-
?
ATP + p38 MAP kinase
ADP + phosphorylated p38 MAP kinase
show the reaction diagram
Mus musculus, Mus musculus C75BL/6
-
GRK2 inactivates and regulates MAP kinase p38 modulating p38-dependent physiological processes, p38 and GRK2 are localized in a multimolecular complex
-
-
?
ATP + PDEgamma
ADP + phosphorylated PDEgamma
show the reaction diagram
-
phosphorylation of PDEgamma possibly stimulates EGFR-mediated ERK activation
-
-
?
ATP + PDGFRbeta
ADP + phosphorylated PDGFRbeta
show the reaction diagram
-
-
-
-
?
ATP + phosducin
ADP + phosphorylated phosducin
show the reaction diagram
-
phosducin is activated to inhibit Gbetagamma protein
-
-
?
ATP + platelet-derived growth factor receptor-beta
ADP + phosphorylated platelet-derived growth factor receptor-beta
show the reaction diagram
-
feedback inhibition mechanism, overview
-
-
?
ATP + protein
ATP + phosphoprotein
show the reaction diagram
-
specifically phosphorylates the agonist-occupied forms of the beta 2-adrenergic receptor and related G protein-coupled receptors
-
-
?
ATP + protein
ATP + phosphoprotein
show the reaction diagram
P25098
the enzyme mediates agonist-dependent phosphorylation of the beta 2-adrenergic and related G protein-coupled receptors
-
-
?
ATP + protein
ATP + phosphoprotein
show the reaction diagram
P26818
specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors
-
-
?
ATP + protein M33
ADP + phosphorylated protein M33
show the reaction diagram
-
GRK2 is a potent regulator of the mouse cytomegalovirus GPCR protein M33-induced Gq/11 signaling through its ability to phosphorylate M33 and sequester Galphaq/11 proteins dependent on an intact RH domain, the protein M33 is able to induce inositol phosphate accumulation, activate NF-kappaB, and promote smooth muscle cell migration, viral GPCRs like M33 play a role in viral dissemination in vivo, M33 is required for efficient murine cytomegalovirus replication in the mouse, and induces several signlaing pathways, overview
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
-
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
-
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
P26819
-
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
light-activated rhodopsin
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
light-activated rhodopsin
-
-
?
ATP + ribosomal protein P2
ADP + phosphorylated ribosomal protein P2
show the reaction diagram
-
activation of P2
-
-
?
ATP + Smo
ADP + phosphorylated Smo
show the reaction diagram
-
GPRK2 participates in Hedgehog signaling in Drosophila melanogaster, and plays a key role in the Smo signal transduction pathway, when Gprk2 levels are lowered, Smo still accumulates at the cell membrane, but its activation is reduced, overview
-
-
?
ATP + Smoothened protein
ADP + phosphorylated Smoothened
show the reaction diagram
-
GRK2 promotes smoothened signal transduction involved in regulation of cellular proliferation and differentiation through activation of the transcription factor Gli, overview
-
-
?
ATP + synuclein
ADP + phosphorylated synuclein
show the reaction diagram
-
-
-
-
?
ATP + [beta2-adrenergic receptor]
ADP + [beta2-adrenergic receptor] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [TSH receptor]
ADP + [TSH receptor]phosphate
show the reaction diagram
-
GRK2 and GRK3, receptor activation
-
-
?
ezrin + ATP
phosphorylated ezrin + ADP
show the reaction diagram
-
-
-
-
?
histamine H2 receptor + ATP
phosphorylated histamine H2 receptor + ADP
show the reaction diagram
-
-
-
-
?
radixin + ATP
phosphorylated radixin + ADP
show the reaction diagram
-
-
-
-
?
moesin + ATP
phosphorylated moesin + ADP
show the reaction diagram
-
-
-
-
?
additional information
?
-
P21146
enzyme is important in mediating rapid agonist-specific desensitization
-
-
-
additional information
?
-
-
role for beta ARK in modulating some receptor-mediated immune functions
-
-
-
additional information
?
-
P26817, P26819
general role in the desensitization of synaptic receptors
-
-
-
additional information
?
-
-
Gprk2 is required for egg morphogenesis
-
-
-
additional information
?
-
-
beta-ARK is probably a general adenylate cyclase-coupled receptor kinase
-
-
-
additional information
?
-
-
beta-ARK 1 is a key regulatory enzyme involved in the regulation of G protein-coupled receptors which associate with microsomal and plasma membranes
-
-
-
additional information
?
-
-
plays a pivotal role in phosphorylating and desensitizing G protein-coupled receptors by vitue of pleckstrin homology domain-mediated membrane translocation
-
-
-
additional information
?
-
-
beta-ARK activity is regulated by endogenous G proteins in different intracellular locations
-
-
-
additional information
?
-
-
phosphorylates and regulates receptors coupled to either stimulation or inhibition of adenylate cyclase
-
-
-
additional information
?
-
P26817, P26819
general function in desensitizing of many G protein-coupled receptor systems
-
-
-
additional information
?
-
-
involved in the regulation of G protein-coupled receptor function, beta-ARK 1 appears to be the predominant GRK in early embryogenesis and plays a fundamental role in cardiac development, enzyme participates in intracellular signal transduction mechanisms, which regulate cardiogenesis
-
-
-
additional information
?
-
-
adenovirus-mediated overexpression of phosphoinositide 3-kinase restore contractile function of cardiac myocytes isolated from failing hearts, the recombinant PIK replaces the endogenous PIK in the transgenic pigs, the endogenous PIK shows abnormally increased activity in complex with betaARK1, overview
-
-
-
additional information
?
-
-
betaARK enhances the contractility in heart myocardium via inhibition of Gbetagamma subunits
-
-
-
additional information
?
-
-
betaARK1 binds phosphoinositide 3-kinase, which is by this way targeted to agonist-stimulated beta-adrenergic receptors, where it regulates endocytosis, disruption of the betaARK1-PIK complex leads to restoration of beta-adrenergic receptor signaling and contractile function in heart failure, overview
-
-
-
additional information
?
-
-
betaARK1 inhibition improves beta-adrenergic signaling and contractile function in failing human myocytes
-
-
-
additional information
?
-
-
brain death induction, as well as sham-operation of pigs, lead to uncoupling of the beta-adrenergic receptor with acutely increased myocardial beta-adrenergic receptor kinase activity leading to left ventricular dysfunction
-
-
-
additional information
?
-
-
dopamine D3 receptor binds to G proteins, the coupling is regulated by the filamin expression level
-
-
-
additional information
?
-
-
G protein-coupled receptors are involved in the regulation of diverse physiological processes, mechanisms of G protein-coupled receptor desensitization, e.g. by phosphorylation or feedback inhibition, overview
-
-
-
additional information
?
-
-
GRK2 and GRK3 are involved in methacholine-stimulated inositol 3-phosphate production
-
-
-
additional information
?
-
-
GRK2 expression plays a role in the fly development, GRK2 expression is required in the germline for proper formation of the anterior egg structures, egg hatching, and for early and late embryogenesis
-
-
-
additional information
?
-
-
GRK2 is involved in A2 adenosine receptor response to agonists
-
-
-
additional information
?
-
-
GRK2 mediates endothelin-1-induced insulin resistance via the inhibition of both Galphaq/11 and insulin receptor substrate-1 pathways in 3T3-L1 adipocytes, GRK2 does not affect insulin receptor tyrosine phosphorylation
-
-
-
additional information
?
-
-
GRK2 regulation mechanism of ERK activation involving interaction with mitogen-activated protein kinase, GRK2 diminishes the level of activating phosphorylation of ERK by CCL2 binding to chemokine receptor CCR2 in endothelial cells
-
-
-
additional information
?
-
-
GRK3 is essential for induction of germinal vesicle breakdown, GRK3 forms a complex with beta-arrestin-2 causing G protein-coupled receptor desensitization
-
-
-
additional information
?
-
-
GRKs are involved in diverse physiological processes and pathologies, overview
-
-
-
additional information
?
-
-
phosphorylation of heptahelical receptors by GRK2 is a universal regulatory mehanism leading to desensitization of G protein signaling and to the activation of alternative signaling pathways
-
-
-
additional information
?
-
-
the enzyme is involved in G protein-coupled receptor signal transduction pathways and desensitization, GRK2 is a multiple domain kinase regulating by multiple mechanisms, overview
-
-
-
additional information
?
-
-
adrenal GRK2 upregulation mediates sympathetic overdrive in heart failure, adrenal gland-specific GRK2 inhibition reverses alpha2 beta-adrenergic receptor dysregulation in heart failure, resulting in lowered plasma catecholamine levels, improved cardiac beta-adrenergic signaling and function, and increased sympatholytic efficacy of a alpha2 beta-adrenergic agonist
-
-
-
additional information
?
-
-
GPCR-dependent kinases play a major role in agonist-induced phosphorylation and desensitization of G-protein coupled receptors, GRK2 is a component of neuronal and glial fibrillary tau deposits with no preference in tau isoform binding, GRK2 may play a role in hyperphosphorylation of tau in tauopathies
-
-
-
additional information
?
-
-
GRK activity is regulated by phosphorylation through several kinases and by interactions with several cellular proteins, e.g. calmodulin, caveolin or RKIP, GRK also interacts with PI3K, Akt, GIT or MEK, the interactions occur at the RH and PH domains, overview, the GRK interactome: role of GRKs in GPCR regulation and signaling, detailed overview
-
-
-
additional information
?
-
-
GRK-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling and desensitization, beta-arrestin-mediated receptor internalization, activity of GRKs and subcellular targeting is tightly regulated by interaction with receptor domains, G protein subunits, lipids, anchoring proteins and calcium-sensitive proteins, selective binding of activated Galphaq and Galpha-11 to RH domains of GRK2 and GRK3 selectively inhibits Gq signaling
-
-
-
additional information
?
-
-
GRK2 activity leads to translocation of parts of beta-adrenergic receptors to endocytic vesicles
-
-
-
additional information
?
-
-
GRK2 interacts with multiple signaling proteins and is involved in several cellular processes, e.g. expression and regulation of key cardiac seven-transmembrane receptors, 7TM receptors, such as the beta-adrenergic and angiotensin receptors, GRK2 interacts with NCS-1, mechanism, overview, GRK2 inhibition can ameliorate heart failure, molecular mechanism of GRK2 activity regulation, GRK2 is probably involved in regulation of hypertension, overview
-
-
-
additional information
?
-
-
GRK2 is essential, and GRK2-deficient mice are embryonically lethal
-
-
-
additional information
?
-
-
GRK2 negatively regulates glycogen synthesis in mouse liver FL83B cells, regulates basal and insulin-stimulated glycogen synthesis via a post-IR signaling mechanism, and GRK2 may contribute to reduced IR expression and function during chronic insulin exposure
-
-
-
additional information
?
-
-
GRK2 plays a role in sodium transport regulation and is involved in the development of essential hypertension, overview
-
-
-
additional information
?
-
-
GRK2 regulates 7TM G-protein-coupled receptor activity, GRK2 promotes the association between active Smoothened and beta-arrestin 2, overview
-
-
-
additional information
?
-
O97627
insulin-mediated dopamine D1 receptor desensitization and underlying molecular mechanism in opossum kidney cells, overview
-
-
-
additional information
?
-
-
G protein-coupled receptor kinases and arrestins are key participants in the canonical pathways leading to phosphorylation-dependent G protein-coupled receptor, GPCR, desensitization, endocytosis, intracellular trafficking and resensitization as well as in the modulation of important intracellular signaling cascades by GPCR, structure-function relationships, overview. GRK activity is tightly modulated by mechanisms including phosphorylation by different kinases and interaction with several cellular proteins such as calmodulin, caveolin or RKIP. Different mechanisms of signalling pathways modulation by GRK2, and regulation of GRK2, overview
-
-
-
additional information
?
-
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
-
additional information
?
-
-
Gprk2, a Drosophila member of the G protein-coupled receptor kinases, plays a key role in the Smo, i.e. Smoothened, signal transduction pathway, overview. When Gprk2 levels are lowered, Smo still accumulates at the cell membrane, but its activation is reduced. Regulation of Gprk2 expression by Hh signaling in the wing disc, but Gprk2 is also required for Hh signaling in the wing disc, overview
-
-
-
additional information
?
-
-
GRK-mediated desensitization of beta2-adrenergic receptors is sufficient to cause declines in cAMP signals. GRK-mediated desensitization is primarily responsible for a sustained suppression of beta2AR signaling, overview
-
-
-
additional information
?
-
P26819
GRK2 causes enhanced catecholamine secretion by desensitizing sympatho-inhibitory alpha2-adrenergic receptors of chromaffin cells and thereby aggravating heart failure
-
-
-
additional information
?
-
-
GRK2 in cardiac myocytes catalyzes phosphorylation and desensitization of different G protein-coupled receptors through specificity controlled by their carboxyl-terminal pleckstrin homology domain, overview
-
-
-
additional information
?
-
Q3UYH7
GRK2 is important for myocardial regulation, and is up-regulated in the dysfunctional heart
-
-
-
additional information
?
-
P26819
GRK2 substrate specificity in adult rat cardiac myocytes, overview. GRK2 completely lacks the capacity to attenuate phenylephrine-stimulated IP generation
-
-
-
additional information
?
-
-
GRK3 in cardiac myocytes catalyzes phosphorylation and desensitization of different G protein-coupled receptors through specificity controlled by its carboxyl-terminal pleckstrin homology domain. GRK3 controls cardiac alpha1-adrenergic receptor responsiveness, distinct functions of GRK3 in regulation of cardiac contractility and growth, overview
-
-
-
additional information
?
-
P26819
GRK3 substrate specificity in adult rat cardiac myocytes, overview
-
-
-
additional information
?
-
-
carboxyl-terminus of GRK2 interacts with Hsp90. Reactive oxygen species (ROS)-mediated mitochrondrial localisation of GRK2 is dependent on Hsp90 binding
-
-
-
additional information
?
-
-
Gprk2 interacts with the Drosophila IkB homolog Cactus
-
-
-
additional information
?
-
-
GRK2 interacts with Hsp90. Reactive oxygen species (ROS)-mediated mitochrondrial localisation of GRK2 is dependent on Hsp90 binding
-
-
-
additional information
?
-
Mus musculus C75BL/6
-
GRK2 is essential, and GRK2-deficient mice are embryonically lethal
-
-
-
additional information
?
-
Mus musculus C75BL/6
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
-
Mg2+
-
optimal concentration: 2-6 mM; requirement
Mg2+
-
requirement
Mg2+
-
as MgATP2-
Mg2+
-
increases binding of beta-ARK to microsomal membranes
Mg2+
-
-
Mn2+
-
requirement, can replace Mg2+ with 50% efficiency, optimal concentration: 1-3 mM
Mn2+
-
Mn2+ can partially substitute Mg2+ in increasing the binding of beta-ARK to microsomal membranes
additional information
-
not activated by Ca2+, Co2+ or Zn2+
additional information
-
no activation by Ca2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2,3-diphosphoglycerate
-
weak
2,3-diphosphoglycerate
-
inhibits in the millimolar range, IC50: 1.1 mM with rhodopsin as substrate; weak
4-amino-1-tert-butyl-3-(1'-naphthyl)pyrrazolo[3,4-d]pyrimidine
-
i.e. 1-Na-PP1, inhibits mutant C221V mediated morphine-induced internalization of the micro-opioid receptor, but not wild-type GRK2 and mutant L271G activities
59-74E
-
-
-
Actin
-
-
-
actinin
-
inhibits GRK2
-
actinin
-
-
-
alpha-actinin
-
-
alpha2-adrenergic antagonist
-
co-incubation completely blocks phosphorylation of alpha2-adrenergic receptor
-
Alprenolol
-
beta-adrenergic antagonist, blocks phosphorylation
atropine
-
receptor antagonist
balanol
-
-
-
betaARKct
-
the isolated C-terminal sequence of the enzyme acts as a peptide inhibitor
-
betaARKct
P26819
a GRK2 inhibitor
-
betaARKct
-
-
-
betaARKct
-
injection of betaARKct is associated with decreased levels of betaARK1 at 7, 14, and 21 days
-
C-terminus of beta-ARK
-
betaARKmini, inhibits
-
Ca2+
-
inhibits GRK2
Ca2+/calmodulin
-
inhibit GRK2 with an IC50 of about 0.002 mM, inhibition mechanism via direct binding
-
Ca2+/calmodulin
-
-
-
Calmodulin
-
-
calveolin
-
-
-
caveolin
-
microsomal anchor protein, inhibits GRK2
-
caveolin
-
-
-
Chloropromazine
-
IC50: 0.043 mM
chondroitin sulfate B
-
weak
chondroitin sulfate C
-
less inhibitory than heparin
concanavalin A
-
inhibitor of clathrin-mediated receptor endocytosis via clathrin binding domain of beta-arrestin-2, inhibitor reduces the GRK3/beta-arrestin-2 induction activity of germinal vesicle breakdown
-
corticotropin-releasing factor
-
reduces GRK2 expression in pituitary cells, suppressed by astressin, opposite effect compared to corticotroph tumor cells AtT20
-
D-glucosamine 2,6-disulfate
-
inhibits in the millimolar range, weak, IC50: 7.3 mM with rhodopsin as substrate
D-Sphingosine
-
IC50: 0.027 mM
Dextran sulfate
-
strong, IC50: 0.00015 mM with rhodopsin as substrate
-
Digitonin
-
IC50: 0.05 mM
Digitonin
-
0.05-0.1%, 93-95% inhibition
GRK2ct
-
C-terminal portion of GRK2
-
GRK2ct
-
GRK2 inhibitor GRK2ct corresponding to the carboxyl-terminal 194 amino acids of GRK2 is expressed in failing cardiac fibroblasts using an adenoviral-mediated approach driven by the CMV promoter. Inhibition restores beta-agonist stimulated inhibition of collagen synthesis and decreases collagen synthesis in response to TGF beta stimulation
-
Heparan sulfate
-
less inhibitory than heparin
heparin
-
most potent inhibitor to date
heparin
-
rhodopsin phosphorylation, in a dose-dependent manner
heparin
P35626
-
heparin
-
de-N-sulfated heparin is 8fold less effective; most potent inhibitor to date; polylysine, spermine or spermidine at lower concentrations partially reverses; strong, kinetics, IC50: 0.00003 mM with beta-AR as substrate, 0.00015 mM with rhodopsin as substrate
heparin
-
0.001 mM, complete inhibition of muscarinic cholinergic receptor phosphorylation
heparin
-
beta-ARK 1: IC50 is 0.0014 mM, beta-ARK 2: IC50 is 0.0011 mM; inhibits both isozymes ARK1 and ARK2 potently with IC50 of 0.0014 mM and 0.0011 mM, respectively; most potent inhibitor to date
heparin
-
specific inhibitor, 1 mM/l: almost complete inhibition of rhodopsin phosphorylation
heparin
-
potent inhibitor of beta-ARK 1
Inositol hexaphosphate
-
weak, IC50: 3.6 mM with rhodopsin as substrate
Inositol hexasulfate
-
good inhibitor; IC50: 0.0135 mM with rhodopsin as substrate
Inositol hexasulfate
-
270fold more potent than inositol hexaphosphate; IC50: 0.0135 mM with rhodopsin as substrate
McN-A343
-
weak, partial antagonist
NaCl
-
0.1 M, 90% inhibition
NaCl
-
20 mM, 48% inhibition, as efficient as F-, I-, NO2- or acetate, less efficient than citrate, phosphate or sulfate
NaF
-
as efficient as Cl-, I-, NO2- or acetate, less efficient than citrate, phosphate or sulfate
NaI
-
as efficient as Cl-, F-, NO2- or acetate, less efficient than citrate, phosphate or sulfate
NaNO2
-
as efficient as Cl-, I-, F- or acetate, less efficient than citrate, phosphate or sulfate
nitric oxide
-
inhibits GRK2 by S-nitrosylation at Cys340, regulatory function of S-nitrosylation
peptide
-
synthetic peptides from a variety of intracellular regions of beta2-AR specifically inhibit phosphorylation of the intact receptor, but not of peptide substrates
peptide
-
synthetic peptides derived from the receptor intracellular loop inhibit
phosphatidylinositol 4,5-bisphosphate
-
inhibits receptor phosphorylation, causes membrane association, 30% inhibition of phosphorylation of RRREEEEESAAA
Polyaspartic acid
-
good inhibitor; IC50: 0.0013 mM with rhodopsin as substrate
Polyaspartic acid
-
IC50: 0.0013 mM with rhodopsin as substrate
Polyglutamic acid
-
good inhibitor
Polyglutamic acid
-
IC50: 0.002 mM with rhodopsin as substrate
polylysine
-
IC50: 0.069 mM with rhodopsin as substrate
polylysine
-
IC50: 0.069 mM with rhodopsin as substrate; weak, more potent than spermine and spermidine
propranolol
-
beta-adrenergic antagonist, in presence no phosphorylation
Protein kinase C inhibitor H7
-
IC50: 0.25 mM; weak
-
Protein kinase C inhibitor H7
-
weak
-
pyridoxal 5'-phosphate
-
weak, IC50: 0.9 mM with rhodopsin as substrate
pyridoxal 5'-phosphate
-
inhibits in the millimolar range; weak, IC50: 0.9 mM with rhodopsin as substrate
quinpirole
-
inhibits GRK2 and GRK3
Raf kinase inhibitor protein
-
RKIP
-
rhodopsin
-
intact light-activated rhodopsin slightly inhibits phosphorylation of RRREEEEESAAA
RKIP
-
-
-
RNA aptamer C13
-
development and synthesis of a highly specific RNA aptamer C13 that potently inhibits GRK2 by binding to it kinase domain, binding kinetics, inhibitor secondary structure, overview
-
S-nitrosothiols
-
inhibit GRK2 by S-nitrosylation at Cys340, regulatory function of S-nitrosylation
-
Sangivamycin
-
IC50: 0.067 mM
Sodium acetate
-
as efficient as Cl-, I-, NO2- or F-, less efficient than citrate, phosphate or sulfate
Sodium citrate
-
20 mM, 97% inhibition, more efficient than phosphate, sulfate, Cl-, F-, I-, NO2- or acetate
Sodium phosphate
-
20 mM, 76% inhibition, less efficient than citrate, as good as sulfate, more efficient than Cl-, F-, I-, NO2- or acetate
Sodium sulfate
-
less efficient than citrate, as good as phosphate, more efficient than Cl-, F-, I-, NO2- or acetate
spermidine
-
weak, less potent than polylysine
spermine
-
IC50: 1.6 mM; weak, less potent than polylysine
spermine
-
weak, less potent than polylysine
tamoxifen
-
IC50: 0.04 mM
Trifluoperazine
-
IC50: 0.035 mM
Triton X-100
-
IC50: 0.054 mM
Tween 20
-
IC50: 0.027 mM
Yohimbine
-
alpha2-adrenergic antagonist, co-incubation completely blocks phosphorylation of alpha2-adrenergic receptor
Zn2+
-
0.1-0.2 mM ZnCl2, 94-98% inhibition
monodansyl cadaverin
-
inhibitor of clathrin-mediated receptor endocytosis via clathrin binding domain of beta-arrestin-2, inhibitor reduces the GRK3/beta-arrestin-2 induction activity of germinal vesicle breakdown
additional information
-
autoregulation by a pseudosubstrate mechanism, overview
-
additional information
-
-
-
additional information
-
not inhibited by protein kinase A inhibitor PKI; not inhibited by staurosporine
-
additional information
-
not inhibited by cAMP, cGMP, cAMP-dependent protein kinase inhibitor, Ca2+/calmodulin, Ca2+/phospholipid, phorbol esters
-
additional information
-
alprenolol is no inhibitor with alpha2-adrenergic receptor as substrate
-
additional information
-
not affected by Ca2+ or Co2+
-
additional information
-
not inhibited by staurosporine
-
additional information
-
marked inhibition of rhodopsin or synthetic peptide phosphorylation in the presence of increasing amounts of microsomal membranes, bound enzyme is less able to interact with its substrate
-
additional information
-
phosphorylation by ERK1/2 inhibits GRK2
-
additional information
-
clathrin inhibitors inhibit the internalization of the beta-adrenergic receptor by GRK
-
additional information
-
deletion mutants of the enzyme, comprising parts of the C-terminus or the N-terminus, are able to inhibit the full-length wild-type enzyme, overview
-
additional information
-
platelet-derived growth factor receptor-beta activates the enzyme by tyrosine phosphorylation, the wild-type PDGFRbeta is 60fold more active with GRK2 than PDGFRbeta mutant Y857F, GRK2 activation also increases GRK2 degradation and downregulation
-
additional information
-
isolated pleckstrin homology domains of GRK2 and GRK3 can act as enzyme inhibitors preventing interaction of the enzymes with the G protein subunits
-
additional information
-
quantitative determination of S-nitrosylation of GRK2 by the biotin-switch assay
-
additional information
-
ERK phosphorylates and inhibits GRK2, protein kinase C phosphorylated GRK2 at Ser685 and induces RKIP binding, RKIP binds to GRK2 and inhibits it after it has been phosphorylated by protein kinase C
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(-)-Epinephrine
-
requirement, agonist, alpha2-adrenergic receptor as substrate
AlF4-
-
enhances beta-ARK activity upon stimulation of heterotrimeric G proteins
alpha2A-adrenergic receptor
-
epinephrine-activated alpha2A-adrenergic receptor activates GRK2, interaction with GRK2 via the second and third intracellular loop of the receptor, determination of regions required for specific interaction utilizing recombinant GST-tagged wild-type and several mutant alpha2A ARs, residues R225, R226, R218, K320, R322, and K358 are important, overview
-
arrestins
-
arrestins modulate the enzyme activity having a regulatory role, regulation of arrestins, overview
-
beta-arrestin
-
required for phosphorylation activity and receptor substrate endocytosis
-
beta-arrestin-2
-
required, membrane protein
-
beta-arrestin-2
-
forms a complex with GRK3 causing G protein-coupled receptor desensitization
-
beta-arrestin2
-
mediates GRK activity, forms a signaling complex with filamin and dopamine D3 receptor, interactions, overview
-
beta2-adrenergic receptor
-
interaction of enzyme with human agonist-occupied receptor specifically and significantly enhances peptide phosphorylation, at lower concentrations, enhances both the affinity and catalytic efficiency for peptide phosphorylation
-
beta2-adrenergic receptor
-
interaction of beta-ARK 1 with the agonist-occupied receptor activates
-
cAMP-dependent protein kinase
-
PKA-mediated phosphorylation favors subsequent phosphorylation of beta2-AR by beta-ARK, PKA increases the phosphorylation rate of beta-ARK
-
Carbachol
-
requirement, agonist, muscarinic cholinergic receptor as substrate
cardiolipin
-
activates, phosphorylation of beta2-AR
corticotropin-releasing factor
-
induces GRK2 expression in pituitary cells, suppressed by astressin, opposite effect compared to pituitary cells
-
G protein
-
GRK2 binds G protein beta1gamma2 subunits, binding structure, no correct complex formation with recombinant Gbetagamma mutant C68S lacking the isoprenylation site, overview
-
G protein
-
binding and modulation of GRK2 and GRK3, Gbetagamma subunits bind GRK2 required for lipid association and G protein-coupled receptor phosphorylation and are released afterwards
-
G protein
-
interaction via GRK2 N-terminal RGS domain, binding of free Gbetagamma subunits initiates GRK2 translocation from cytosol to the plasma membrane and its activation for receptor phosphorylation
-
G protein
-
required for GRK2 activation
-
G protein
-
binding of Gbeta/gamma dimers, activation is required for translocation from cytosol to plasma membrane
-
G protein
-
GRK2 binds G protein beta1gamma2 subunits, binding structure, overview
-
G protein betagamma-subunit
-
10fold activation, beta-ARK 1 and 2, increases incorporation of phosphate from 4 to 10 mol phosphate/mol receptor
-
G protein betagamma-subunit
-
activates, binding domain is localized to the C-terminal region of beta-ARK; from brain, binds to the C-terminal half of the PH domain
-
G protein betagamma-subunit
-
from bovine brain, beta-ARK 1 and 2: requirement, selectivity for betagamma subunits, both isoforms differentiate between defined betagamma subunits
-
G protein betagamma-subunit
-
requirement, binding plays an important role in specifically targeting the enzyme complex to its receptor substrate
-
G protein betagamma-subunit
-
from brain, stimulates the phosphorylation of rhodopsin, but not of the peptide RRREEEEESAAA, an intact N-terminus of the gamma subunit is required for stimulation, but not for kinase binding, endoprotease Lys-C blocks stimulation, Gbetagamma binds to the C-terminal region of beta-ARK containing the pleckstrin homology domain, role of the G protein gamma-subunit
-
G protein betagamma-subunit
-
activates, binding domain is localized to the C-terminal region of beta-ARK
-
G protein betagamma-subunit
-
required for maximum activity, targets beta-ARK 1 to the membrane, which presumably facilitates the precise orchestration of phosphorylation of only activated receptors
-
G protein betagamma-subunit
-
-
-
G protein Gbetagamma subunits
-
activate both ARK1 and ARK2 about 2.5fold
-
G protein Gbetagamma subunits
-
required for activity, 20fold stimulation with substrate rhodopsin, 2 regulatory Gbetagamma binding sites: one N-terminal domain of GRK2, and one C-terminal within the pleckstrin homology domain, both sites are functionally different, overview
-
Gbetagamma subunits
-
required for activity on G protein-coupled receptors, binding via enzyme C-terminal pleckstrin homology domain, binding does not induce large domain rearrangements, but small rotations of the enzyme domains, the domain interfaces remain intact upon GRK2 activation, structure analysis of GRK2 in complex with G protein beta1gamma2 subunits, overview
-
Insulin
O97627
leads to increase dopamine D1 receptor serine phosphorylation by GRK2
-
Insulin
-
initiates GRK2 membrane translocation
-
isoproterenol
-
requirement, beta-agonist, beta-adrenergic receptor as substrate
isoproterenol
-
requirement, beta-agonist, beta-adrenergic receptor as substrate
isoproterenol
-
requirement, beta-agonist, beta-adrenergic receptor as substrate
isoproterenol
-
stimulates
Oxytremorine
-
requirement, agonist, muscarinic cholinergic receptor as substrate
phosphatidic acid
-
activates, phosphorylation of beta2-AR
phosphatidylglycerol
-
activates, phosphorylation of beta2-AR
phosphatidylinositol
-
activates, phosphorylation of beta2-AR, 6fold activation of phosphorylation of RRREEEEESAAA
phosphatidylinositol 4,5-bisphosphate
-
binding of GRK2 and GRK3 via their pleckstrin homology domains, activate the phosphorylation activity
phosphatidylserine
-
activates, phosphorylation of beta2-AR
phosphatidylserine
-
binding of GRK2 and GRK3 via their pleckstrin homology domains, activate the phosphorylation activity
Phospholipid
-
required for phosphorylation of beta2-AR, activation is associated with a conformational change in beta-ARK 1, acidic phospholipid specificity, not activated by phosphatidylinositol 4,5-diphosphate, direct regulation of beta-ARK 1 activity by phospholipids
PIP2
-
activates GRK2 through binding to its PH domain
Platelet activating factor
-
requirement, agonist, beta-adrenergic receptor as substrate
platelet-derived growth factor receptor-beta
-
activates the enzyme by tyrosine phosphorylation at Y13, Y86, and Y92, required, the wild-type PDGFRbeta is 60fold more active with GRK2 than PDGFRbeta mutant Y857F, GRK2 activation also increases GRK2 degradation and downregulation, independent of Gbetagamma subunits and phosphoinositide 3-kinase
-
rhodopsin
-
interaction of enzyme with light-activated rhodopsin or truncated rhodopsin lacking its C-terminal phosphorylation sites activates peptide phosphorylation, at lower concentrations, enhances both the affinity and catalytic efficiency for peptide phosphorylation, but intact light-activated rhodopsin slightly inhibits the phosphorylation of RRREEEEESAAA
mastoparan/guanosine 5'-(3-O-thio)triphosphate
-
enhances beta-ARK activity upon stimulation of heterotrimeric G proteins
-
additional information
-
autoregulation by a pseudosubstrate mechanism, overview
-
additional information
-
not activated by polycations; partial agonists promote reduced receptor phosphorylation
-
additional information
-
not activated by cAMP, cGMP, Ca2+/calmodulin, Ca2+/phospholipid, phorbol esters
-
additional information
-
alpha2-AR phosphorylation is not stimulated by isoproterenol
-
additional information
-
not effected by Ca2+ or Co2+
-
additional information
-
agonists induce specific conformational changes allowing phosphorylation
-
additional information
-
myocardial ischemia: beta-ARK is activated, rapid induction of beta-ARK 1 activity in membranes, presumably caused by the release of the receptor agonist noradrenaline
-
additional information
-
phosphorylation by c-Src activates GRK2
-
additional information
-
phosphorylation activates the enzyme
-
additional information
-
GRK2 is activated by phosphorylation through kinases c-SRC, PKA and PKC, and it is activated by phospholipids
-
additional information
-
GRK2 is activated by phosphorylation through c-Src in a positive feedback reaction, Hsp90 secures proper folding and maturation and protects GRK2 from ubiquitination and proteasomal degradation, it induces GRK2 expression, phosphoinositol kinase 3 binds GRK2 and enhances receptor internalization
-
additional information
-
GRK3 bind the Gbetagamma subunit complex, a process that induces activation of the GRKs by phosphorylation
-
additional information
-
activation of Toll-like receptors significantly increases GRK2 expression in primary macrophages, mechanism, overview
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.017
-
ATP
-
pH 7.8, 23C, recombinant wild-type GRK2, with substrate tubulin
0.022
-
ATP
-
pH 7.5, 30C, recombinant beta-ARK 1, rhodopsin as substrate
0.033
-
ATP
-
pH 7.5, 30C, beta-adrenergic receptor as substrate
0.037
-
ATP
-
pH 7.5, 30C, rhodopsin as substrate
0.06
0.09
ATP
-
MgATP2-, beta-ARK 1 and 2
0.062
-
ATP
-
pH 7.8, 23C, recombinant GRK2 L271G mutant, with substrate tubulin
0.149
-
ATP
-
pH 7.8, 23C, recombinant GRK2 C221V mutant, with substrate tubulin
0.00025
-
beta-adrenergic receptor
-
pH 7.5, 30C
-
0.9
1.3
peptide
-
acid-rich synthetic peptides
1.5
4.8
peptide
-
synthetic peptides containing a single Glu-residue
0.0038
-
rhodopsin
-
pH 7.5, 30C, recombinant beta-ARK 1
0.0053
-
rhodopsin
-
pH 7.4, 30C, in absence of heparin
0.006
-
rhodopsin
-
pH 7.5, 30C
0.014
-
rhodopsin
-
beta-ARK 1 and 2; isozymes ARK1 and ARK2
5.1
-
RRRAEASAA
-
pH 7.4, 30C, recombinant beta-ARK 1
3.3
-
RRRASAAASAA
-
pH 7.4, 30C, recombinant beta-ARK 1
5.4
-
RRRASASAA
-
pH 7.4, 30C, recombinant beta-ARK 1
4.6
-
RRRASpAAASAA
-
pH 7.4, 30C, recombinant beta-ARK 1
3.4
-
RRRASpASAA
-
pH 7.4, 30C, recombinant beta-ARK 1
0.72
-
RRREEEEESAAA
-
pH 7.4, 30C, recombinant beta-ARK 1
-
1.34
-
RRREEEEESAAA
-
pH 7.4, 30C, recombinant beta-ARK 1
-
0.06
0.09
MgATP2-
-
isozymes ARK1 and ARK2
additional information
-
additional information
-
kinetics of isozymes ARK1 and ARK2
-
additional information
-
additional information
-
kinetics of peptide phosphorylation, influence of activated rhodopsin and beta2-AR on the Km value for different peptide substrates
-
additional information
-
additional information
-
kinetics
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0001
-
ATP
-
pH 7.8, 23C, recombinant GRK2 L271G mutant, with substrate tubulin
0.0029
-
ATP
-
pH 7.8, 23C, recombinant wild-type GRK2, with substrate tubulin
0.0041
-
ATP
-
pH 7.8, 23C, recombinant GRK2 C221V mutant, with substrate tubulin
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00015
-
heparin
-
-
additional information
-
additional information
-
-
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.1
-
2,3-diphosphoglycerate
-
inhibits in the millimolar range, IC50: 1.1 mM with rhodopsin as substrate
5e-05
-
balanol
-
pH 7.4, 20C
-
0.002
-
Ca2+/calmodulin
-
inhibit GRK2 with an IC50 of about 0.002 mM, inhibition mechanism via direct binding
-
0.043
-
Chloropromazine
-
IC50: 0.043 mM
7.3
-
D-glucosamine 2,6-disulfate
-
inhibits in the millimolar range, weak, IC50: 7.3 mM with rhodopsin as substrate
0.027
-
D-Sphingosine
-
IC50: 0.027 mM
0.00015
-
Dextran sulfate
-
strong, IC50: 0.00015 mM with rhodopsin as substrate
-
0.05
-
Digitonin
-
IC50: 0.05 mM
3e-05
-
heparin
-
strong, kinetics, IC50: 0.00003 mM with beta-AR as substrate, 0.00015 mM with rhodopsin as substrate
0.0011
-
heparin
-
beta-ARK 1: IC50 is 0.0014 mM, beta-ARK 2: IC50 is 0.0011 mM
0.0014
-
heparin
-
inhibits both isozymes ARK1 and ARK2 potently with IC50 of 0.0014 mM and 0.0011 mM, respectively
3.6
-
Inositol hexaphosphate
-
weak, IC50: 3.6 mM with rhodopsin as substrate
0.0135
-
Inositol hexasulfate
-
IC50: 0.0135 mM with rhodopsin as substrate
0.0013
-
Polyaspartic acid
-
IC50: 0.0013 mM with rhodopsin as substrate
0.002
-
Polyglutamic acid
-
IC50: 0.002 mM with rhodopsin as substrate
0.069
-
polylysine
-
IC50: 0.069 mM with rhodopsin as substrate
0.25
-
Protein kinase C inhibitor H7
-
IC50: 0.25 mM
-
0.9
-
pyridoxal 5'-phosphate
-
weak, IC50: 0.9 mM with rhodopsin as substrate
4.1e-06
-
RNA aptamer C13
-
inhibition of GRK2, kinetics, overview
-
0.067
-
Sangivamycin
-
IC50: 0.067 mM
1.6
-
spermine
-
IC50: 1.6 mM
0.04
-
tamoxifen
-
IC50: 0.04 mM
0.035
-
Trifluoperazine
-
IC50: 0.035 mM
0.054
-
Triton X-100
-
IC50: 0.054 mM
0.027
-
Tween 20
-
IC50: 0.027 mM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00873
-
-
pH 7.5, 30C
0.05
0.08
-
pH 7.5, 30C
1
-
-
about, recombinant beta-ARK 1, expressed in SF9 cells
additional information
-
-
beta-ARK 2 has a 25% lower specific activity than beta-ARK 1 towards rhodopsin and beta2-AR
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
P26819
quantitative enzyme level determination
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
7.5
-
-
7
-
-
assay at
7.3
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.5
-
-
assay at
7.5
-
P26817, P26819
assay at; assay at
7.5
-
-
assay at
7.5
-
-
assay at
7.8
-
-
assay at
8
-
P26819
assay at; assay at
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20
-
-
assay at
22
-
-
assay at room temperature
22
-
-
assay at room temperature
23
-
-
assay at
25
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
P26817, P26819
assay at; assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at, rhodopsin phosphorylation by recombinant mutant beta-ARK
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
37
-
-
assay at, intact cell phosphorylation of muscarinic receptor subtype 2 and alpha2-adrenergic receptor by recombinant mutant beta-ARK
37
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
beta-ARK 2 has a higher isoelectric point than beta-ARK 1
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
i.e. AT1 cells, from transdifferentiation of AT2 cells
Manually annotated by BRENDA team
-
i.e. AT2 cells, primary cells, transdifferentiation to AT1 cells
Manually annotated by BRENDA team
-
GRK2, no expression of GRK3
Manually annotated by BRENDA team
-
corticotroph tumor cell line, GRK2, no expression of GRK3
Manually annotated by BRENDA team
-
; cerebral cortex; highest beta-ARK mRNA concentrations in brain and spleen, brain: highest levels in cerebral cortex and cerebellum, with significant lower levels in basal ganglia, brain stem, pituitary and hypothalamus
Manually annotated by BRENDA team
P26817, P26819
regional and cellular distribution of beta-ARK 1 and 2 in brain; regional and cellular distribution of beta-ARK 1 and 2 in brain; synapses; synapses
Manually annotated by BRENDA team
P26817
beta-ARK mRNA is expressed intensely in the cerebellar granule cell layer and moderately in the hippocampal pyramidal cells and dentate granule cells. The neocortex and piriform cortex express it moderately to weakly, whereas the thalamus and hypothalamus express it weakly to faintly. No significant expression of the mRNA is detected in the caudate-putamen. Weak expression of beta-ARK mRNA in several nuclei of the brainstem and in the spinal gray matter
Manually annotated by BRENDA team
-
cerebral cortex; highest beta-ARK activity in cerebral cortex
Manually annotated by BRENDA team
-
40-50% co-localization of GRK2 with neurofibrillary tangles in Alzheimer's disease
Manually annotated by BRENDA team
-
H9c2 cardiomyolbasts, ATCC CRL 1446
Manually annotated by BRENDA team
-
brain: highest beta-ARK mRNA concentrations in cerebral cortex and cerebellum
Manually annotated by BRENDA team
-
brain: highest beta-ARK mRNA concentrations in cerebral cortex and cerebellum
Manually annotated by BRENDA team
-
highest beta-ARK activity
Manually annotated by BRENDA team
-
whole embryo extract
Manually annotated by BRENDA team
-
analysis of GRK2 localization in alveolar epithelium
Manually annotated by BRENDA team
-
a hepatocyte cell line
Manually annotated by BRENDA team
-
about 40% of beta-ARK mRNA concentration in brain
Manually annotated by BRENDA team
-
moderate expression of beta-ARK 1
Manually annotated by BRENDA team
P35626
moderate expression of beta-ARK 2
Manually annotated by BRENDA team
-, Q64682
enhanced expression of beta-adrenergic receptor kinase 1 in the hearts of cardiomyopathic Syrian hamsters, BIO53.58; significantly increased expression of beta-ARK 1 in the hearts of BIO53.58 hamsters compared to control hamsters F1b
Manually annotated by BRENDA team
-
beta-ARK 1 is the predominant myocardial GRK
Manually annotated by BRENDA team
-
during myocardial ischemia the membrane activity of beta-ARK is increased
Manually annotated by BRENDA team
-
adult heart
Manually annotated by BRENDA team
-
GRK3 expression is not increased in heart failure
Manually annotated by BRENDA team
-
distribution of GRK2 in mouse myocardial tissue, overview; distribution of GRK3 in mouse myocardial tissue, overview
Manually annotated by BRENDA team
-
high expression of beta-ARK 1
Manually annotated by BRENDA team
P35626
beta-ARK 2
Manually annotated by BRENDA team
-
high expression of beta-ARK 1
Manually annotated by BRENDA team
-
about 20% of beta-ARK mRNA concentration in brain
Manually annotated by BRENDA team
-
myeloid and lymphoid leukemia cell lines, high expression of beta-ARK 1
Manually annotated by BRENDA team
-
beta-ARK 1; mononuclear, peripheral blood leukocytes, high expression; peripheral blood leukocytes
Manually annotated by BRENDA team
-
beta-ARK 2
Manually annotated by BRENDA team
P35626
beta-ARK 2; mononuclear, peripheral blood leukocytes, high expression; peripheral blood leukocytes
Manually annotated by BRENDA team
-
about 40% of beta-ARK mRNA concentration in brain
Manually annotated by BRENDA team
P35626
moderate expression of beta-ARK 2
Manually annotated by BRENDA team
-
analysis of GRK2 localization in alveolar epithelium, determination of expression level
Manually annotated by BRENDA team
-
GRK2 is increased in hypertension
Manually annotated by BRENDA team
-
peritoneal macrophages, activation of Toll-like receptors significantly increases GRK2 expression in primary macrophages, mechanism, overview
Manually annotated by BRENDA team
Mus musculus C75BL/6
-
; peritoneal macrophages, activation of Toll-like receptors significantly increases GRK2 expression in primary macrophages, mechanism, overview
-
Manually annotated by BRENDA team
-
myocardial G protein-coupled receptor kinase expression and activity, overview
Manually annotated by BRENDA team
-
primary isolated from hearts of patients in the end-stage of heart failure undergoing heart transplantation
Manually annotated by BRENDA team
-
cardiac myocytes isolated from failing hearts
Manually annotated by BRENDA team
P26817, P26819
beta-ARK 1 and 2 are expressed primarily in neurons distributed throughout the CNS; beta-ARK 1 and 2 are expressed primarily in neurons distributed throughout the CNS
Manually annotated by BRENDA team
-
colocalization of GRK2 and tau in intracellular neurofibrillary tangles and isolated paired helical filaments
Manually annotated by BRENDA team
O97627
a renal proximal tubular cell line
Manually annotated by BRENDA team
-
about 20% of beta-ARK mRNA concentration in brain
Manually annotated by BRENDA team
-
kin- mutant cell line of S49 lymphoma cells
Manually annotated by BRENDA team
-
neuroblastoma cell line
Manually annotated by BRENDA team
-
DDT-MF2 smooth muscle cells derived from ductus deferens leiomyosarcoma
Manually annotated by BRENDA team
-
highest beta-ARK mRNA concentrations in brain and spleen
Manually annotated by BRENDA team
-
increased expression of GRK3 in hyperfunctioning thyroid nodule
Manually annotated by BRENDA team
-
prepared without lymphocytic infiltrations in the tumor, GRKs expression patterns, low expression of GRK2, and high expression level of GRK3
Manually annotated by BRENDA team
-
high expression of beta-ARK 1
Manually annotated by BRENDA team
-
an osteosarcoma cell line
Manually annotated by BRENDA team
-
GRK2 is increased in hypertension
Manually annotated by BRENDA team
-
high expression of beta-ARK 1
Manually annotated by BRENDA team
additional information
-
ubiquitous enzyme
Manually annotated by BRENDA team
additional information
-
not in liver, muscle and adrenal gland; tissue distribution
Manually annotated by BRENDA team
additional information
-
-
Manually annotated by BRENDA team
additional information
-
tissue distribution of beta-ARK 1
Manually annotated by BRENDA team
additional information
-
tissue distribution of beta-ARK 2
Manually annotated by BRENDA team
additional information
P35626
tissue distribution of beta-ARK 2
Manually annotated by BRENDA team
additional information
-
tissue distribution; ubiquitous enzyme
Manually annotated by BRENDA team
additional information
-
GRK2 expression analysis in different developmental stages, the expression is required in the germline
Manually annotated by BRENDA team
additional information
-
GRK2 and GRK3 are expressed in a wide variety of tissues, expression patterns, overview
Manually annotated by BRENDA team
additional information
-
analysis of GRK2 expression rate and mRNA level in heart and lymphocytes by RT-PCR
Manually annotated by BRENDA team
additional information
-
GRK2 and GRK3 are ubiquitously expressed in mammalian tissues
Manually annotated by BRENDA team
additional information
-
Lewy bodies were negative for both GRK2 and GRK5 in Lewy body disease
Manually annotated by BRENDA team
additional information
P26819
quantitative enzyme level determination
Manually annotated by BRENDA team
additional information
-
the enzyme is ubiquitously expressed, developmental regulation of GRK2 expression, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
predominantly cytoplasmic, enzyme activity depends upon its translocation from the cytoplasm to the membrane, the betagamma subunits of G proteins bind to enzyme and recruit it to the membrane, beta-ARK 1 binds to Gbeta2
Manually annotated by BRENDA team
-
cytosolic enzyme, isoproterenol and platelet-activating factor induce translocation of beta-ARK from cytosol to membrane
Manually annotated by BRENDA team
-
in unstimulated cells enzyme is mainly located in the cytosol
Manually annotated by BRENDA team
-
cardiac, total cytosolic activity amount to values almost 3times those of membrane activity, during myocardial ischemia the membrane activity of beta-ARK is increased, but the cytosolic activity is not altered
Manually annotated by BRENDA team
-
GRK2 translocation from cytosol to the plasma membrane
Manually annotated by BRENDA team
-
isoproterenol and platelet-activating factor induce translocation of beta-ARK from cytosol to membrane
Manually annotated by BRENDA team
-
enzyme activity depends upon its translocation from the cytoplasm to the membrane, the betagamma subunits of G proteins bind to enzyme and recruit it to the membrane, beta-ARK 1 binds to Gbeta2
Manually annotated by BRENDA team
-
enzyme is localized to the specific membrane compartment by betagamma subunits of G proteins and phosphatidylinositol phosphates that specifically and coordinately bind to the C- and N-terminal half, respectively, of the PH domain
Manually annotated by BRENDA team
-
after beta-AR agonist stimulation beta-ARK is partially translocated to the membranes
Manually annotated by BRENDA team
-
microsomal and plasma membrane, anchoring of beta-ARK to cellular membranes under basal conditions is independent of the availability of heterotrimeric G protein subunits, additional anchoring mechanisms, Gbetagamma subunits may play a role in agonist-mediated targeting of beta-ARK to the membrane in intact cells
Manually annotated by BRENDA team
-
the PH domain ligands betagamma subunits of G proteins and phosphatidylinositol 4,5-bisphosphate affect membrane localization of enzyme, simultaneous presence of both ligands is required for effective membrane localization, cooperative binding of the ligands, membrane translocation
Manually annotated by BRENDA team
-
cardiac, total cytosolic activity amount to values almost 3times those of membrane activity, during myocardial ischemia the membrane activity of beta-ARK is increased, but the cytosolic activity is not altered
Manually annotated by BRENDA team
-
G protein betagamma-subunit targets beta-ARK 1 to the membrane
Manually annotated by BRENDA team
-
associated with, membrane association is required for activity on G protein-coupled receptors, and mediated by the C-terminal Gbetagamma binding domain
Manually annotated by BRENDA team
-
associated, GRK2 in complex with G protein beta1gamma2 subunits
Manually annotated by BRENDA team
O97627
insulin causes GRK2 translocation to the membranes, which is blocked by genistein, wortmannin, chelerythrine chloride, and GRK2-specific siRNA
Manually annotated by BRENDA team
-
GRK2 membrane translocation is induced by insulin
Manually annotated by BRENDA team
-
myocardial sarcolemmal membrane
Manually annotated by BRENDA team
-
microsomal membranes
-
Manually annotated by BRENDA team
-
associates with intracellular microsomal membranes, mechanism, modulation of binding of enzyme, main determinants of binding appear to be localized to an 60 amino acid residue stretch, residues 88 to 145, G protein betagamma subunits are not the main anchor in the membranes
-
Manually annotated by BRENDA team
-
beta-AR may serve as membrane anchor for enzyme, translocation of beta-ARK from the cytosol to the plasma membrane
Manually annotated by BRENDA team
-
soluble enzyme, that transiently translocates to the plasma membrane
Manually annotated by BRENDA team
-
GRK2 and GRK3, transient translocation upon G protein-coupled receptor activation
Manually annotated by BRENDA team
-
transient recruitment of GRK2 and GRK3 after GPCR activation, the enzymes bind via pleckstrin homology domains to phosphoinositol-4,5-bisphosphate in the plasma membrane
Manually annotated by BRENDA team
-
the wild-type GRK2 is translocated to the plasma membrane
Manually annotated by BRENDA team
-
recruitment of GRk2 to the plasma membrane is assisted by phospholipids and Gbetagamma proteins binding to the PH domain and another N-terminal site
Manually annotated by BRENDA team
-
predominantly
-
Manually annotated by BRENDA team
-
soluble enzyme, that transiently translocates to the plasma membrane
-
Manually annotated by BRENDA team
-
after myocardial ischemic and oxidative stress there is increased mitochondrial GRK2 translocation
Manually annotated by BRENDA team
additional information
P26817, P26819
subcellular distribution of beta-ARK 1 and 2; subcellular distribution of beta-ARK 1 and 2
-
Manually annotated by BRENDA team
additional information
-
subcellular distribution of beta-ARK 1
-
Manually annotated by BRENDA team
additional information
-
complex modulation of the subcellular distribution of beta-ARK
-
Manually annotated by BRENDA team
additional information
P26819
subcellular distribution analysis of GRK2 and GRK3
-
Manually annotated by BRENDA team
additional information
Q3UYH7
GRK2 is not located in the nucleus
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
77000
-
P26817, P26819
beta-ARK 2, Western blot analysis
80000
-
-
gel filtration
80000
-
-
expected size of native beta-ARK; Western blot analysis
80000
-
-
Western blot analysis
80000
-
-
Western blot analysis
80000
-
-
Western blot analysis
82000
-
P26817, P26819
beta-ARK 1, Western blot analysis
additional information
-
-
amino acid sequences of human and bovine beta-ARK 1 and 2
additional information
-
P35626
amino acid sequences of human and bovine beta-ARK 1 and 2
additional information
-
-
beta-ARK 1: amino acid sequence, 689 amino acids protein
additional information
-
-
equilibrium sedimentation measurements on GRK2-Gbetagamma complexes, overview
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 79700, calculated from the amino acid sequence; x * 80000, SDS-PAGE
?
P26817, P26819
x * 79800, predicted from the amino acid sequence; x * 79900, predicted from the amino acid sequence
?
-
x * 80000, recombinant GRK2, gel filtration and SDS-PAGE
?
-
x * 80000, GRK2, SDS-PAGE
?
-
x * 80000, GRK2 catalytic domain, domain structure, overview
?
P26819
x * 79000, GRK3, SDS-PAGE, x * 81000, GRK2, SDS-PAGE
monomer
-
1 * 80000, SDS-PAGE
additional information
-
GRK2 consists of 3 modular domains: a predominantly N-terminal RGS homology domain, a central protein kinase domain, and a C-terminal pleckstrin homology domain, the interfaces of the domains are important for stability, and enzyme expression and activity, and remain intact upon GRK2 activation, structure analysis of GRK2 in complex with G protein beta1gamma2 subunits, overview
additional information
-
betaARK subfamily multidomain structure, overview
additional information
-
GRK3 wild-type and mutant domain structures, overview
additional information
-
GRK family domain structure, the N-terminal RGS domain of GRK2 has regulatory function on G protein binding and receptor phosphorylation and activity, overview
additional information
-
GRK2 consists of 3 modular domains: a predominantly N-terminal RGS homology domain, a central protein kinase domain, and a C-terminal pleckstrin homology domain, domain functions, overview
additional information
-
domain structure of GRK2, overview
additional information
P26819
GRK2 consists of three domains: an aminoterminal RGS homology domain, a central protein kinase domain, and a carboxyl-terminal pleckstrin homology, PH, domain; GRK3 consists of three domains: an aminoterminal RGS homology domain, a central protein kinase domain, and a carboxyl-terminal pleckstrin homology, PH, domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
enzyme appears to autophosphorylate
phosphoprotein
-
GRK2 is phosphorylated by MAP kinase at S670
phosphoprotein
-
epinephrine-activated alpha2A-adrenergic receptor activates GRK2, interaction with GRK2 via the second and third intracellular loop of the receptor, determination of regions required for specific interaction and phosphorylation activity utilizing recombinant GST-tagged wild-type and several mutant alpha2A ARs, residues R225, R226, R218, K320, R322, and K358 are important, overview
phosphoprotein
-
-
phosphoprotein
-
GRK2 is phosphorylated by c-Src kinase, ERK1 and ERK2, protein kinase C, and PKA, overview
phosphoprotein
-
phosphorylation, e.g. by PKA, PKC, ERK1/2 or c-SRC, activates the enzyme
phosphoprotein
-
GRK2 is activated by phosphorylation through c-Src, while phosphorylation by ERK inhibits GRK2
phosphoprotein
-
GRKs are regulated by phopshorylation
phosphoprotein
-
GRK2 is phosphorylated by c-Src kinase, ERK1 and ERK2, protein kinase C, and PKA, overview
phosphoprotein
-
GRK2 is phosphorylated by c-Src kinase, ERK1 and ERK2, protein kinase C, and PKA, overview
phosphoprotein
-
-
additional information
-
no autophosphorylation of beta-ARK 1
phosphoprotein
-
phosphorylated at Ser670
additional information
-
mechanisms of regulation of GRK protein stability and degradation, e.g. via ubiquitination or protease cleavage, overview
phosphoprotein
-
autophosphorylation, the site often depends more on structure than on primary sequence
additional information
-
mechanisms of regulation of GRK protein stability and degradation, e.g. via ubiquitination or protease cleavage, overview
additional information
-
GRK2 is ubiquinated after being tyrosine phosphorylated leading to its proteolytic degradation via the ubiquitine/proteasome pathway, regulation overview
phosphoprotein
-
regulation of GRKs by other kinases, such as PKA, PKC, ERK1 and ERK2, e.g. GRK2 is phosphorylated at Ser670 by ERK1 or ERK2, phosphorylation of the beta-adrenergic receptor-activated GRK2 by c-SRC at tyrosine residues mediated by binding of beta-arrestin, which rapidly activates the GPCR phosphorylation activity of GRK2 and its degradation via the ubiquitine/proteosome pathway, overview
additional information
-
mechanisms of regulation of GRK protein stability and degradation, e.g. via ubiquination or protease cleavage, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purified recombinant GRK2 in complex with purified recombinant bovine G protein beta1gamma2 subunits, two-dimensional hanging drop vapor diffusion method screen, 0.001 ml protein solution containing 5-20% PEG3350 versus pH 5.0-7.5, 1 M NaCl, 12 mg/ml protein, mixed with 0.001 ml of well solution containing 0.1 M MES, pH 5.25, 0.2 M NaCl, 1 mM inositol-3,4,5-trisphosphate, 5 mM MgCl2, and 6.9-7.8% PEG3350, versus 1 ml of well solution, inositol-3,4,5-trisphosphate can be substituted by EDTA and phosphatidylserine, both crystal types diffract differently but show identical unit-cell parameters, X-ray diffraction structure determination and analysis at 3.2 A resolution, Cu Kalpha radiation
-
purified recombinant GRK2 in complex with purified recombinant G protein beta1gamma2 subunits, X-ray diffraction structure determination and analysis at 2.5 A resolution, modeling
-
purified recombinant GRK2 S670A mutant, hanging drop vapour diffusion method, 4C, 0.002 ml protein solution containing 15 mg/ml GRK2, 20 mM HEPES, pH 8.0, 0.2 M NaCl, and 2 mM DTT, mixed with 0.002 ml well solution containing 0.1 M HEPES, pH 7.5-8.0, 1 M NaCl, 1 M urea, 10-40 mM phosphoserine, pH 7.0, 5% v/v glycerol, and 9.5-11.5% PEG 8000, 2-3 weeks, X-ray diffraction structure determination and analysis at 4.5 A resolution
-
crystal structures of human GRK2 in complex with Gbetagamma in the presence and absence of the AGC (protein kinase A, kinase G, and kinase C subfamily) kinase inhibitor balanol is determined. Balanol stabilizes the kinase domain of GRK2 in a slightly more closed conformation distinct from that of the protein kinase A balanol complex
-
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Triton X-100 stabilizes
-
glycerol stabilizes
-
ORGANIC SOLVENT
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Triton X-100
-
stabilizes
Triton X-100
-
0.02%; stabilizes
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, purified recombinant His-tagged wild-type and mutant GRK2s, 50 mM NaH2PO4, pH 8.0, 300 mM NaCl, 250 mM imidazole, 30% glycerol, stable for 2 months
-
4C, crude enzyme: several months, stable, purified enzyme: t1/2 of 5-10 days
-
4C, in presence of Triton X-100, 1 year, stable
-
4C, several months, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
20300fold, to near homogeneity
-
about 20000fold, from brain
-
expression in COS 7 cells
P26818
partial
-
recombinant ARK1 and ARK2 from Sf9 insect cells by sequential chromatography, including heparin affinity chromatography; recombinant beta-ARK 1 and 2 overexpressed in Sf9 cells
-
recombinant beta-ARK 1 and 2 overexpressed in Sf9 cells
-
recombinant beta-ARK 1 expressed in Sf9 cells
-
recombinant beta-ARK expressed in Sf9 cells
-
recombinant GRK2 from Spodoptera frugiperda Sf9 cells to near homogeneity by ultracentrifugation, 3 steps of cation exchange chromatography, heparin affinity chromatography, another ion exchange chromatography step, and gel filtration, the recombinant His6-tagged G protein beta1gamma2 subunits by solubilization from membranes, Ni2+ affinity and ion exchange chromatography, and gel filtration
-
recombinant His-tagged wild-type and mutant GRK2s from Spodoptera frugiperda Sf9 cells by nickel affinity chromatography
-
recombinant beta-ARK 1, expressed in Sf9 cells
-
recombinant GRK2 from insect Sf9 cells by ammonium sulfate fractionation, hydrophobic interaction and heparin affinity chromatography
-
recombinant GST-tagged GRK2 and GRK2 C-terminal or N-terminal domains from insect Sf9 cells by ion exchange and heparin affinity chromatography
-
recombinant GST-tagged wild-type and truncation mutant GRK2s from Escherichia coli by glutathione affinity chromatography, recombinant wild-type GRK2 from Sf9 insect cells by heparin affinity chromatography and gel filtration
-
partial, 50-100fold, from kin- mutants of S49 lymphoma cells
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
adenovirus-mediated expression of beta-adrenergic receptor kinase C-terminus in pigs in endothelial cells and smooth muscle cells, overview
-
beta-ARK 1 and 2 are cloned and expressed in SF9 cells using the baculovirus expression system
-
beta-ARK 1 and 2 are cloned and expressed in SF9 cells using the baculovirus expression system; overexpression of ARK1 and ARK2 in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
beta-ARK 1 is cloned and expressed in SF9 cells using the baculovirus expression system
-
beta-ARK 1 is cloned and expressed in SF9 cells using the baculovirus expression system; cloning of GST-beta-ARK fusion proteins and expression in Escherichia coli AG1
-
beta-ARK 1 is cloned and expressed in yeast strain L40
-
beta-ARK 1 is stably overexpressed in HEK-293 cells
-
beta-ARK expression in SF9 cells
-
carboxyl-terminus is expressed as a Flag-tagged betaARKct (GRK2 amino acids 495-689) in HeLa and HEK293 cells
-
cDNA encoding beta-ARK is cloned from brain, sequenced and expressed in COS-7 cells, cDNA encodes a 689 amino acids protein; expression in COS-7 cells
-
co-overexpression of GRK2 and G protein beta1gamma2 subunits in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
co-overexpression of GRK2 and His6-tagged G protein beta1gamma2 subunits in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
co-overexpression of GRK2 mutants and G protein beta1gamma2 subunits in Spodoptera frugiperda Sf9 cells using the baculovirus infection system, and in COS-1 cells
-
expresed in HEK293T cells and COS7 cells
-
expression of GRK2 in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
expression of HA-tagged GRK2 wild-type and mutants and of FLAG-tagged platelet-derived growth factor receptor-beta wild-type and mutants in HEK-293 cells
-
expression of wild-type and mutant GRK2 in C3H10T1/2 cells, transient expression in HEK-293 cells, expression of GRK2, but not catalytically inactive GRK2, synergizes with active Smoothened to mediate Gli-dependent transcription
-
expression of wild-type GRK2 and mutants in HEK-293 cells, co-expression of GRK2 and CCR2B produces a 65-70% reduction for the wild-type GRK2 and 52% for the mutant GRK2 K220R in ERK phosphorylation by inhibition of CCL2
-
functional GRK2 overexpression in transgenic mice, tissue-specific transgenic mRNA expression analysis, tissue-specific overexpression of GRK2 in mouse osteoblasts by usage of the osteocalcin gene-2 promoter
-
overexpression of GRK2 in HEK-293 cells and in COS-7 cells, co-expression with FLAG-tagged dopamine D3 receptor, and filamin A and/or beta-arrestin, recombinant beta-arrestin is accumulated in the plasma membrane in presence of GRK2 and absence of agonist
-
stable co-expression of C-terminally HA-tagged wild-type GRK2 and murine micro-opioid receptor in HEK-293 cells, transient expression of C-terminally HA-tagged wild-type and mutant GRK2s in HEK-293 cells, expression of His-tagged wild-type and mutant GRK2s in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
transient overexpression of wild-type GRK2 in NG108-15 mouse neuroblastoma x rat glioma hybrid cells
-
very similar cDNA sequences of bovine and human kinases
-
wild-type beta-ARK 1 is expressed in SF9 and COS-7 cells, mutant beta-ARK 1 is cloned and expressed in COS-7 cells
-
expression of GRK2-fusion constructs in transgenic flies, expression analysis, overview
-
adenovirus-mediated gene transfer and expression of inhibitor betaARKct in primary myocytes isolated from hearts of patients in the end-stage of heart failure undergoing heart transplantation, betaARK1 activity is inhibited but beta-adrenergic signaling and contractile function are improved
-
beta ARK locus segregated with the long arm of chromosome 11, centromeric to 11q13
-
beta-ARK 1 is cloned and expressed in SF9 cells using the baculovirus expression system
-
cDNA encoding beta-ARK 1 is cloned and sequenced, very similar sequences of bovine and human kinases; cloning and sequencing
-
cDNA encoding beta-ARK 2 is cloned, expressed in COS-7 cells and sequenced; expression in COS7 cells; very similar sequences of bovine and human kinases
P35626
co-expression of rat thyrotropin receptor with GRK2 and GRK3 in HEK-293 cells, receptor phosphorylation occurs with both enzymes
-
DNAs encoding the C-terminal domains Gly556-Ser670 and Pro466-Leu689 are cloned and expressed in Escherichia coli
-
expressed in NG-108-15 cells
-
expressed in Sf9 clls using the baculovirus expression system
-
expression of GRK2 in Spodoptera frugiperda Sf9 cells
-
expression of GRK2, with or without inhibitor GRK2ct, in vascular smooth emuscle of transgenic mice, phenotypes, overview
-
expression of GST-tagged GRK2 and GRK2 C-terminal or N-terminal domains in Spodoptera frugiperda Sf9 cells using the baculovirus transfection method
-
expression of GST-tagged wild-type and truncation mutant GRK2s in Escherichia coli, expression of wild-type GRK2 in Spodoptera frugiperda Sf9 cells using the baculovirus infection system, expression of wild-type and truncation mutant GRK2s in HEK-293 cells
-
expression of kinase-dead GRK2 mutant and of the N-terminal region of GRK2, residues Ala2-Thr187, in HEK-293 cells
-
expression of wild-type and mutant GRK2
-
overexpression of the C-terminus of betaARK in ventricular cardiomyocytes and in the myocardium of rabbits suffering heart failure by adenoviral gene transfer, co-expression of N-terminal deletion mutant of phosducin, leading to increase in contractility of the cells due to inhibition of Gbetagamma subunits rather than to beta-adrenergic receptor resensitization, betaARK additionally stimulates cAMP production
-
overexpression of wild-type and kinase-dead mutant GRK2 in murine 3T3-L1 adipocytes via adenovirus infection system leading to inhibition of Galphaq/11 signaling, including tyrosine phosphorylation of Galphaq11 and cdc42-associated phosphatidylinositol 3-kinase activity, overexpression of the inactive muant, but not of wild-type enzyme, inhibits endothelin-1-induced Ser612 phosphorylation of insulin receptor substrate-1, and restores activation of the pathway
-
regulation of GRK2 expression, analysis, overview
-
stable overexpression of GFP-fusion K220R mutant GRK2 and GFP-fusion K220R mutant GRK3 in SH-SY5Y neuroblastoma cells via adenovirus infection system
-
; cDNA encoding beta-ARK 1 is cloned from heart and sequenced, 689 amino acids protein, 95% homology to rat and 90% homology to human beta-ARK 1
-, Q64682
cloning and disruption of the beta-ARK 1 gene by homologous recombination, effects of gene disruption on the embryos; studies with beta-ARK 1 knockout mice
-
expression of a dominant negative GRK2 mutant in AtT20 cells showing reduced CRFR1 desensitization
-
expression of Myc-tagged wild-type and mutant GRK2s in HEK-293T cells, co-expression with M33 in wild-type and Galphaq/11-/- mouse embryonic fibroblasts, M33 couples directly to the Gq/11 signaling pathway to induce high levels of total inositol phosphates in an agonist-independent manner
-
studies with beta-ARK 1 knockout mice; studies with transgenic mice overexpressing beta-ARK 1
-
transient expression of GRK2 in HEK-293T cells, co-expression with GST-tagged epithelial Na+ channel, and GST-tagged Nedd4 and Nedd4-2
-
cDNAs encoding beta-ARK 1, 689 amino acids, and beta-ARK 2, 688 amino acids, are cloned, expressed in COS-7 cells and sequenced; cDNAs encoding beta-ARK 1, 689 amino acids, and beta-ARK 2, 688 amino acids, are cloned, expressed in COS-7 cells and sequenced
P26817, P26819
co-expression of HA-tagged M1 muscarinic acetylcholine receptor and of GRK2 wild-type and mutants in CHO-K1 cells, suppression of 80% of endogenous GRK2 in HEK293 cells and in hippocampal neurons by antisense construct expression of GRK2, co-expression of wild-type and mutant GRK2s with eGFP-tagged inositol 1,4,5-trisphosphate biosensor eGFP-PHPLCdelta in HEK293 cells
-
cytosolic expression of wild-type and mutant GRK2 in HEK-293 cells, co-expression with the beta-adrenergic receptor
-
expression of GRK2 and GRK3 in cardiac myocytes via adenoviral transfection, overview; expression of minigene encoding peptide inhibitors of GRK2, the C-terminal fragments of GRK2, i.e. AdGRK2, and AdGRK2ct, using adenovirus infection of cardiac myocyte, with effects on rod-shaped morphology of cardiac myocytes, overview; expression of minigene encoding peptide inhibitors of GRK3, the C-terminal fragments of GRK3, i.e. AdGRK3, or AdGRK3ct, using adenovirus infection of cardiac myocyte, with effects on rod-shaped morphology of cardiac myocytes, overview
P26819
expression of GRK2 using an adenoviral expression system in suprerenal glands, the transgene-expression is restricted to the adrenal cortical region, overview
P26819
functional expression of HA-tagged wild-type and mutant GRK3, and coexpression with beta-arrestin-2, in Xenopus laevis oocytes via injection of mRNA, leads to induction of maturation of the oocytes
-
nucleotide sequence of beta-ARK 1, 95% homology to Syrian hamster beta-ARK 1
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
a 4fold increase in GRK2 expression in the failing cardiac fibroblasts is detected compared with normal controls
-
GRK2 protein expression is enhanced under insulin-resistant conditions
-
as heart failure progresses after adenoviral-betaARKct gene delivery, betaARK1 levels progressively increase
-
protein levels of endogenous betaARK1 progressively increase with progression of heart failure
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C221V
-
site-directed mutagenesis, mutant GRK2 activity is slightly increased compared to the wild-type enzyme, the requirement for initial ligand-induced internalization of a G protein-coupled receptor with subsequent rounds of internalization is different for the mutant GRK2 compared to the wild-type enzyme
D110A
-
the mutant shows impaired binding to Galphaq proteins, mutant GRK2 inhibits ERK phosphorylation similar to the wild-type enzyme when co-expressed with CCR2B in HEK-293 cells
D110A
-
the expression of the D110A mutant in COS7-transfected cells fails to desensitize the histamine H2 receptor
D110A/K220R
-
double mutant has a disrupted RGS (regulator of G protein signalling) function. Although double mutant coimmunoprecipitates with the histamine H2 receptor, it reverses GRK2K220R-mediated histamine H2 receptor desensitization
D635K/S636K/D637K
-
triple mutant D635K/S636K/D637K, mutation in the Gbetagamma-binding region of the PH domain
D637K
-
triple mutant D635K/S636K/D637K, mutation in the Gbetagamma-binding region of the PH domain
DELTA495-689
-
carboxyl-terminus is expressed as a Flag-tagged betaARKct (GRK2 amino acids 495-689) in HeLa and HEK293 cells
E520A
-
site-directed mutagenesis, very low recombinant expression level, mutant GRK2 shows a dramatic loss of activity with rhodopsin as substrate
E646K
-
mutation in the Gbetagamma-binding region of the PH domain
E96A
-
site-directed mutagenesis, slightly increased recombinant expression level compared to the wild-type GRK2, mutant GRK2 shows activity with rhodopsin as substrate similar to the wild-type enzyme
K220R
-
mutant GRK2 inhibits ERK phosphorylation in a slightly reduced rate compared to the wild-type enzyme when co-expressed with CCR2B in HEK-293 cells
K220R
-
inactive GRK2 mutant
K220R
-
catalytically inactive mutant. Mutant cells desensitize histamine H2 receptor signaling in the same degree as the GRK2 wild type cells. Although the receptor phosphorylation is crucial for histamine H2 receptor internalization and resensitization, the kinase activity is not required to achieve histamine H2 receptor desensitization
K567E
-
mutation in the PIP2-binding region of the PH domain
K645E
-
mutation in the Gbetagamma-binding region of the PH domain
L271G
-
site-directed mutagenesis, mutant GRK2 shows highly reduced activity compared to the wild-type enzyme
L273Y
-
site-directed mutagenesis, mutant GRK2 shows highly reduced activity compared to the wild-type enzyme
L336F
-
site-directed mutagenesis, mutant GRK2 shows highly reduced activity compared to the wild-type enzyme
P638D
-
site-directed mutagenesis, RH-PH domain interface residue mutant, 40% reduced recombinant expression level compared to the wild-type GRK2, mutant GRK2 shows 15% of wild-type activity with rhodopsin as substrate
Q642G
-
mutation in the Gbetagamma-binding region of the PH domain
R516A
-
site-directed mutagenesis, 60% reduced recombinant expression level compared to the wild-type GRK2, mutant GRK2 shows slightly reduced activity with rhodopsin as substrate
R578N
-
double mutant R578N/R579N, mutation in the PIP2-binding region of the PH domain
R579N
-
double mutant R578N/R579N, mutation in the PIP2-binding region of the PH domain
S636K
-
triple mutant D635K/S636K/D637K, mutation in the Gbetagamma-binding region of the PH domain
S670A
-
site-directed mutagenesis, the MAP kinase phosphorylation site S670 is eliminated in the GRK2 mutant enzyme
S670A
-
cells overexpressing the S670A-GRK2 mutant have less H2O2-induced death as determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In cells expressing mutant GRK2, the amount of cell death is significantly reduced by 36.4%. Mutant displays significantly less Hsp90 binding in myocytes after oxidative stress compared with wild-type GRK2. Nonphosphorylated mutant S670A is not localized to mitochondria after oxidative stress
S670D
-
mutant shows the highest level of interaction with Hsp90 compared to wild-type and mutant S670A
V42E
-
site-directed mutagenesis, RH-PH domain interface residue mutant, 60% reduced recombinant expression level compared to the wild-type GRK2, mutant GRK2 shows 25% of wild-type activity with rhodopsin as substrate
W576A
-
mutation in the PIP2-binding region of the PH domain
W643A
-
residue of the PH domain, mutation completely abolishes beta-ARK activity and activation by the G protein betagamma-subunit
Y13F
-
site-directed mutagenesis, required activating tyrosine phosphorylation by platelet-derived growth factor receptor-beta kinase activity is reduced with the mutant GRK2, reduced activity compared to the wild-type
Y13F/Y86F/Y92F
-
site-directed mutagenesis, required activating tyrosine phosphorylation by platelet-derived growth factor receptor-beta kinase activity is eliminated with the mutant GRK2, reduced activity compared to the wild-type
Y46A
-
site-directed mutagenesis, RH-PH domain interface residue mutant, 80% reduced recombinant expression level compared to the wild-type GRK2, mutant GRK2 shows 50% of wild-type activity with rhodopsin as substrate
Y86F
-
site-directed mutagenesis, required activating tyrosine phosphorylation by platelet-derived growth factor receptor-beta kinase activity is reduced with the mutant GRK2, reduced activity compared to the wild-type
Y86F/Y92F
-
site-directed mutagenesis, required activating tyrosine phosphorylation by platelet-derived growth factor receptor-beta kinase activity is highly reduced with the mutant GRK2, reduced activity compared to the wild-type
D110A
-
the Galphaq binding site mutant of GRK 2 inhibits the inositol phosphate signal significantly less than wild-type GRK2, the mutant GRK 2 D110A still inhibitS inositol phosphate formation by 22.35
D110A/K220R
-
the mutant inhibits the inositol phosphate signal significantly less than wild-type GRK2, but does not differ significantly from wild-type GRK2 in its ability to inhibit calcium-sensing receptor signaling
K220R
-
site-directed mutagenesis, kinase-dead GRK2 mutant, overexpression in HEK-293 cells leads to partially desensitization of G protein-coupled receptor
K220R
-
site-directed mutagenesis, inactive, dominant negative mutants of GRK3 and GRK2, overexpression in SH-SY5Y cells does not influence endogenous M3 muscarinic acetylcholine receptor phosphorylation and desensitization by the endogenous wild-type GRK6, but inhibits methacholine-stimulated inositol 3-phosphate production by 75%
K220R
-
a catalytic site mutant of GRK2, the mutant does not differ significantly from wild-type GRK2 in its ability to inhibit calcium-sensing receptor signaling
S670A
-
the GRK2 mutant shows reduced phosphorylation by ERK and is less degraded
D110A
-
the point mutation within the RH domain abrogates GRK2 sequestration of activated GTP-boundGalphaq/11
D110A/K220R
-
the mutant, which exhibits no RH or kinase activity, is completely defective in its ability to attenuate M33 signaling
K220R
-
inactive GRK2 mutant
K220R
-
the point mutation within the kinase domain inhibits GRK2 catalytic activity
D110A
-
site-directed mutagenesis, GRK2 mutant deficient in Galphaq/11 binding
D110A/K220R
-
site-directed mutagenesis, inactive GRK2 mutant deficient in Galphaq/11 binding
K220R
-
site-directed mutagenesis, kinase-dead mutant of GRK3, the mutant is unable to induce germinal vesicle breakdown
L647G
-
residue of the PH domain, mutation completely abolishes beta-ARK activity and activation by the G protein betagamma-subunit
additional information
-
effects of mutations in the pleckstrin homology domain of beta-ARK on activity, Ala-insertion following Trp-643 completely abolishes beta-ARK activity and activation by the G protein betagamma-subunit
additional information
-
targeted tissue-specific overexpression of GRK2 in mouse osteoblasts attenuates parathyroid hormone receptor PTH signaling, and promotes bone loss with decreased osteoclastic activity and decreased osteoblasts and trabecular bone, equal effects in female and male mice, overview
additional information
-
transient overexpression of wild-type GRK2 in NG108-15 mouse neuroblastoma x rat glioma hybrid cells leads to selective inhibition of A2 adenosine receptor responsiveness, but does not affect secretin-stimulated cyclic AMP accumulation
additional information
-
adenovirus-mediated expression of beta-adrenergic receptor kinase C-terminus reduces intimal hyperplasia and luminal stenosis of arteriovenous polytetrafluoroethylene grafts in pigs
additional information
-
construction of a deletion GRK2 mutant comprising residues 438-689, which does not inhibit ERK phosphorylation when co-expressed with CCR2B in HEK-293 cells
additional information
-
knockdown of endogenous GRK2 by short hairpin RNA significantly reduces signaling in response to the Smoothened agonist SAG and also inhibits signaling induced by an oncogenic Smoothened mutant, Smo M2
additional information
-
to identify the domains responsible for the kinase-independent receptor desensitization, the histamine H2 receptor is co-transfected with constructions encoding the GRK2 RGS-homology domain (RH) and the RH or the kinase domain fused to the pleckstrin homology domain. Results demonstrate that the RH domain of GRK2 is sufficient to desensitize the histamine H2 receptor
Y92F
-
site-directed mutagenesis, required activating tyrosine phosphorylation by platelet-derived growth factor receptor-beta kinase activity is reduced with the mutant GRK2, reduced activity compared to the wild-type
additional information
O97627
expression of GRK2-specific siRNA leads to downregulation of the enzyme
additional information
-
mutant, gprk2(6936) disrupts expression of a putative member of the GRK family, the G protein-coupled receptor kinase 2 gene Gprk2. This mutation affects Gprk2 gene expression in the ovaries and renders mutant females sterile. The mutant eggs contain defects in several anterior eggshell structures that are produced by specific subsets of migratory follicle cells. In addition, rare eggs that become fertilized display severe defects in embryogenesis
additional information
-
isolated mutant grk26936 shows developmental defects throughout the life cycle of the fly, phenotype overview, construction of several transgenic flies expressing grk2 under control of the hsp70 or germline-specific promoter, analysis of germline mosaic
additional information
-
generation of a Gprk2 deficiency, phenotype, overview; lowering Gprk2 levels in the wing disc reduces the expression of Smo targets and causes a phenotype reminiscent of loss of Smo function, phenotype, overview
K220R
-
kinase-dead mutant shows no phosphorylation of ezrin/radixin/moesin (ERM) proteins
additional information
-
construction of betaARKct mutant comprising the C-terminus of the enzyme
additional information
-
construction and expression of a mouse mutant beta-adrenergic receptor lacking the GRK phosphorylation sites in HEK-293 cells, and coexpression of murine GFP-tagged beta-arrestin
additional information
-
construction of deletion mutants comprising residues 1-485, 1-185, 561-689, 1-53, 1-200, or 54-185, analysis of activity with rhodopsin and binding of G protein betagamma subunits, overview
K220R
-
kinase-dead mutant fails to alter Akt activation and GLUT4 membrane translocation in response to insulin
additional information
-
construction of transgenic tissue specific or knockout mice
additional information
-
construction of a phosphorylation-defective CCR2 mutant mice, in the mutant mice GRK2 inhibits ERK activation similar to the wild-type mice, the inhibitory effect is eliminated by co-expression of Galphaq-binding RGS-like RH domain of GRK2 or its Gbetagamma-binding domain
additional information
-
phenotypes of several GRK and arrestin knockout mice mutants and of transgenic mice overexpressing GRK2 or GRK3, overview
additional information
-
homozygous GRK2-deficient mice are embryonically lethal, heterozygous deficient mice show reduced activity an an altered phenotype, overview
additional information
-
construction of GRK2-deficient cells by expression of siRNA leads to increased insulin-induced glycogen synthesis and basal and insulin-stimulated phosphorylation of Ser21 in glycogen synthase kinase-3'alpha, phosphorylation of insulin receptor substrate 1 ia increased in case of GRK2 depletion
additional information
-
construction of transgenic mice expressing mutant GRK2 or deficient in active GRK2, cardiac phenotype with heart failure, overview
additional information
-
construction of transgenic mice with cardiac-restricted expression of a competitive inhibitor of GRK3, i.e. the carboxyl-terminal plasma membrane targeting domain of GRK3 from Rattus norvegicus, show significantly enhanced agonist-stimulated beta1-adrenergic receptor-mediated activation of ERK1/2, but no alterations of cardiac mass or left ventricular dimensions, versus cardiac myocytes from nontransgenic littermate control mice consistent with inhibition of GRK3, overview
additional information
Q3UYH7
cardiac GRK2 overexpression does not augments hypertrophy in vivo, phenotype, overview
K220R
Mus musculus C75BL/6
-
inactive GRK2 mutant
-
additional information
Mus musculus C75BL/6
-
homozygous GRK2-deficient mice are embryonically lethal, heterozygous deficient mice show reduced activity an an altered phenotype, overview
-
K220R
-
site-directed mutagenesis, inactive mutant GRK2
additional information
-
truncated GRK3DELTAC lacking the C-terminal Gbetagamma binding domain is unable to induce germinal vesicle breakdown, and is defective in membrane association
additional information
-
construction of GRK2-depleted hippocampal neurons and expression of a GRK2 mutant deficient in Galphaq/11 binding, overexpression of eGFP-tagged inositol 1,4,5-trisphosphate biosensor eGFP-PHPLCdelta leads to suppression of M1 muscarinic acetylcholine receptor-mediated phospholipase C signaling in hippocampal neurons through a phosphorylation-independent mechanism via binding of Galphaq/11 to the RGS homology domain of the enzyme
additional information
-
mutation of the clathrin-binding motif of GRK2 results in a dominant negative form of GRK2 without affecting kinase activity itself and the ability to interact with beta2-adrenergic receptor, no translocation of beta-adrenergic receptors to endocytic vesicles as well as GRK2 translocation to the plasma membrane with the dominant-negative mutant and mutant GRK2-5A, overview
additional information
P26819
expression of GRK2 using an adenoviral expression system in suprerenal glands, the transgene-expression is restricted to the adrenal cortical region, overview, the method is not useful for effectively manipulating adrenal gland signalling, overview
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
reconstitution of the GRK2-G protein beta1gamma2 subunits complex by mixing in a 2:3 ratio
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
biotechnology
-
engineering of a GRK2 mutant sensitive to a specific inhibitor
diagnostics
-
GRK2 levels in heart and peripheral lymphocytes correlate well, therefore the lymphocytic enzyme level might be a very suitable marker for determination for the sympathetic drive to heart failure during clinical course and treatment of human congestive heart failure patients
medicine
-
effectiveness of in vivo applications of beta-ARK 1-targeted gene therapy at ameliorating heart failure, beta-ARK 1 upregulation often precedes the development of measurable heart failure and may represent an indicator for cardiac injury and potential therapeutic intervention prior to clinical dysfunction; heart failure: therapeutic strategy by manipulating beta-AR signaling, specifically through the inhibition of beta-ARK 1, elevated levels of beta-ARK 1 are an early ubiquitous consequence of myocardial injury
medicine
-
heart failure: therapeutic strategy by manipulating beta-AR signaling, specifically through the inhibition of beta-ARK 1, elevated levels of beta-ARK 1 are an early ubiquitous consequence of myocardial injury