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Literature summary for 2.7.11.15 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
Search for more literature for 2.7.11.15

Activating Compound

Activating Compound Comment Organism Structure
arrestins arrestins modulate the enzyme activity having a regulatory role, regulation of arrestins, overview Mus musculus
G protein binding of Gbeta/gamma dimers, activation is required for translocation from cytosol to plasma membrane Mus musculus

Protein Variants

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

Inhibitors

Inhibitors Comment Organism Structure
Ca2+/calmodulin inhibit GRK2 with an IC50 of about 0.002 mM, inhibition mechanism via direct binding Mus musculus
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

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
 Mus musculus 5829
-
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
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
 Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + beta-adrenergic receptor Mus musculus desensitization of the receptor by GRK2 and GRK3 ADP + phosphorylated beta-adrenergic receptor
-
 ?
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
-
 ?
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

Organism UniProt Comment Textmining
Mus musculus
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
additional information GRK2 is ubiquinated after being tyrosine phosphorylated leading to its proteolytic degradation via the ubiquitine/proteasome pathway, regulation overview Mus musculus
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

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + beta-adrenergic receptor desensitization of the receptor by GRK2 and GRK3 Mus musculus ADP + phosphorylated beta-adrenergic receptor
-
 ?
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
-
 ?
ATP + G protein-coupled receptor the GPCRs possess multiple phosphorylation sites for serine/threonine kinases Mus musculus ADP + phosphorylated G protein-coupled receptor
-
 ?
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 ?
-
 ?
additional information the GRKs are specific for GPCRs and arrestins, overview Mus musculus ?
-
 ?

Synonyms

Synonyms Comment Organism
G protein-coupled receptor kinase 2
-
 Mus musculus
G protein-coupled receptor kinase 3
-
 Mus musculus
GRK2
-
 Mus musculus
GRK3
-
 Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Mus musculus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.002
-
 inhibit GRK2 with an IC50 of about 0.002 mM, inhibition mechanism via direct binding Mus musculus Ca2+/calmodulin