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Literature summary extracted from

  • Kohout, T.A.; Lefkowitz, R.J.
    Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization (2003), Mol. Pharmacol., 63, 9-18.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.11.15 arrestins arrestins modulate the enzyme activity having a regulatory role, regulation of arrestins, overview Mus musculus
2.7.11.15 G protein binding of Gbeta/gamma dimers, activation is required for translocation from cytosol to plasma membrane Mus musculus
2.7.11.16 arrestins arrestins modulate the enzyme activity having a regulatory role, regulation of arrestins, overview Mus musculus
2.7.11.16 additional information autophosphorylation of GRK5 is stimulated by phospholipids, such as phosphatidylinositol-4,5-bisphosphate Mus musculus

Protein Variants

EC Number Protein Variants Comment Organism
2.7.11.15 additional information phenotypes of several GRK and arrestin knockout mice mutants and of transgenic mice overexpressing GRK2 or GRK3, overview Mus musculus
2.7.11.16 additional information phenotypes of several GRK and arrestin knockout mice mutants and of transgenic mice overexpressing GRK4 or GRK5, overview Mus musculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.11.15 Ca2+/calmodulin inhibit GRK2 with an IC50 of about 0.002 mM, inhibition mechanism via direct binding Mus musculus
2.7.11.15 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 Mus musculus
2.7.11.16 Ca2+/calmodulin inhibit GRK5 with an IC50 of 40-50 nM, inhibition mechanism via inducing inhibitory autophosphorylation and blocking of membrane association Mus musculus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.11.15 cytosol
-
Mus musculus 5829
-
2.7.11.15 plasma membrane 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 Mus musculus 5886
-
2.7.11.16 plasma membrane constitutive association, location of GRK4-6 near the activated receptors, covalent attachment by fatty acids to the C-terminus, e.g. palmitoylated GRK4 and GRK6, or by electrostatic interactions with phospholipids, e.g. for GRK5 Mus musculus 5886
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.11.15 Mg2+
-
Mus musculus
2.7.11.16 Mg2+
-
Mus musculus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.11.15 ATP + beta-adrenergic receptor Mus musculus desensitization of the receptor by GRK2 and GRK3 ADP + phosphorylated beta-adrenergic receptor
-
?
2.7.11.15 ATP + G protein-coupled receptor Mus musculus phosphorylation has a regulatory role, regulation of the signal transduction involving GRK2 and beta-arrestin, overview ADP + phosphorylated G protein-coupled receptor
-
?
2.7.11.15 additional information Mus musculus 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 ?
-
?
2.7.11.16 ATP + beta-adrenergic receptor Mus musculus desensitization of the receptor by GRK4, GRK5, and GRK6 ADP + phosphorylated beta-adrenergic receptor
-
?
2.7.11.16 ATP + G protein-coupled receptor Mus musculus phosphorylation has a regulatory role ADP + phosphorylated G protein-coupled receptor
-
?
2.7.11.16 additional information Mus musculus 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 ?
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.7.11.15 Mus musculus
-
-
-
2.7.11.16 Mus musculus
-
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.7.11.15 additional information GRK2 is ubiquinated after being tyrosine phosphorylated leading to its proteolytic degradation via the ubiquitine/proteasome pathway, regulation overview Mus musculus
2.7.11.15 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 Mus musculus
2.7.11.16 lipoprotein GRK4-6 are permanently modulated by fatty acids and/or phospholipids Mus musculus
2.7.11.16 phosphoprotein regulation of GRK5 by phosphorylation through PKC, GRK5 is activated by autophosphorylation, autophosphorylation is stimulated by phospholipids, such as phosphatidylinositol-4,5-bisphosphate, overview Mus musculus

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.11.16 GRK2 by gel filtration from Sf9 cells Mus musculus

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.11.15 ATP + beta-adrenergic receptor desensitization of the receptor by GRK2 and GRK3 Mus musculus ADP + phosphorylated beta-adrenergic receptor
-
?
2.7.11.15 ATP + G protein-coupled receptor phosphorylation has a regulatory role, regulation of the signal transduction involving GRK2 and beta-arrestin, overview Mus musculus ADP + phosphorylated G protein-coupled receptor
-
?
2.7.11.15 ATP + G protein-coupled receptor the GPCRs possess multiple phosphorylation sites for serine/threonine kinases Mus musculus ADP + phosphorylated G protein-coupled receptor
-
?
2.7.11.15 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 Mus musculus ?
-
?
2.7.11.15 additional information the GRKs are specific for GPCRs and arrestins, overview Mus musculus ?
-
?
2.7.11.16 ATP + beta-adrenergic receptor desensitization of the receptor by GRK4, GRK5, and GRK6 Mus musculus ADP + phosphorylated beta-adrenergic receptor
-
?
2.7.11.16 ATP + G protein-coupled receptor phosphorylation has a regulatory role Mus musculus ADP + phosphorylated G protein-coupled receptor
-
?
2.7.11.16 ATP + G protein-coupled receptor the GPCRs possess multiple phosphorylation sites for serine/threonine kinases Mus musculus ADP + phosphorylated G protein-coupled receptor
-
?
2.7.11.16 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 Mus musculus ?
-
?
2.7.11.16 additional information the GRKs are specific for GPCRs and arrestins, overview Mus musculus ?
-
?

Synonyms

EC Number Synonyms Comment Organism
2.7.11.15 G protein-coupled receptor kinase 2
-
Mus musculus
2.7.11.15 G protein-coupled receptor kinase 3
-
Mus musculus
2.7.11.15 GRK2
-
Mus musculus
2.7.11.15 GRK3
-
Mus musculus
2.7.11.16 G protein-coupled receptor kinase 4
-
Mus musculus
2.7.11.16 G protein-coupled receptor kinase 5
-
Mus musculus
2.7.11.16 GRK4
-
Mus musculus
2.7.11.16 GRK5
-
Mus musculus

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.11.15 ATP
-
Mus musculus
2.7.11.16 ATP
-
Mus musculus

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.7.11.15 0.002
-
inhibit GRK2 with an IC50 of about 0.002 mM, inhibition mechanism via direct binding Mus musculus Ca2+/calmodulin
2.7.11.16 0.00004 0.00005 inhibit GRK5 with an IC50 of 40-50 nM, inhibition mechanism via inducing inhibitory autophosphorylation and blocking of membrane association Mus musculus Ca2+/calmodulin