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Literature summary for 2.7.11.15 extracted from
- Role of G-protein-coupled receptor kinase 2 in the heart--do regulatory mechanisms open novel therapeutic perspectives? (2006), Trends Cardiovasc. Med., 16, 169-177.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| 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 | Homo sapiens | |
| PIP2 | activates GRK2 through binding to its PH domain | Homo sapiens |  |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| regulation of GRK2 expression, analysis, overview | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| S670A | the GRK2 mutant shows reduced phosphorylation by ERK and is less degraded | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| alpha-actinin | - |
Homo sapiens | |
| calveolin | - |
Homo sapiens | |
| 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 | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| plasma membrane | recruitment of GRk2 to the plasma membrane is assisted by phospholipids and Gbetagamma proteins binding to the PH domain and another N-terminal site | Homo sapiens | 5886 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | - |
Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + angiotensin receptor | Homo sapiens | phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview | ADP + phosphorylated angiotensin receptor | - |
? | |
| ATP + beta-adrenergic receptor | Homo sapiens | phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview | ADP + phosphorylated beta-adrenergic receptor | - |
? | |
| ATP + epithelial Na+ channel | Homo sapiens | channel inactivation | ADP + phosphorylated epithelial Na+ channel | - |
? | |
| ATP + ezrin | Homo sapiens | phosphorylation of ezrin affects the 7TM receptor mediated cytoskeletal reorganization | ADP + phosphorylated ezrin | - |
? | |
| ATP + PDEgamma | Homo sapiens | phosphorylation of PDEgamma possibly stimulates EGFR-mediated ERK activation | ADP + phosphorylated PDEgamma | - |
? | |
| ATP + PDGFRbeta | Homo sapiens | - |
ADP + phosphorylated PDGFRbeta | - |
? | |
| ATP + phosducin | Homo sapiens | phosducin is activated to inhibit Gbetagamma protein | ADP + phosphorylated phosducin | - |
? | |
| ATP + ribosomal protein P2 | Homo sapiens | activation of P2 | ADP + phosphorylated ribosomal protein P2 | - |
? | |
| ATP + synuclein | Homo sapiens | - |
ADP + phosphorylated synuclein | - |
? | |
| additional information | Homo sapiens | 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 | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | GRK2 is activated by phosphorylation through c-Src, while phosphorylation by ERK inhibits GRK2 | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| cardiac myocyte | - |
Homo sapiens | - |
| heart | - |
Homo sapiens | - |
| HEK-293 cell | - |
Homo sapiens | - |
| HL-60 cell | - |
Homo sapiens | - |
| JURKAT cell | - |
Homo sapiens | - |
| lymphocyte | - |
Homo sapiens | - |
| additional information | the enzyme is ubiquitously expressed, developmental regulation of GRK2 expression, overview | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + angiotensin receptor | - |
Homo sapiens | ADP + phosphorylated angiotensin receptor | - |
? | |
| ATP + angiotensin receptor | phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview | Homo sapiens | ADP + phosphorylated angiotensin receptor | - |
? | |
| ATP + beta-adrenergic receptor | - |
Homo sapiens | ADP + phosphorylated beta-adrenergic receptor | - |
? | |
| ATP + beta-adrenergic receptor | phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview | Homo sapiens | ADP + phosphorylated beta-adrenergic receptor | - |
? | |
| ATP + epidermal growth factor receptor | - |
Homo sapiens | ADP + phosphorylated epidermal growth factor receptor | - |
? | |
| ATP + epithelial Na+ channel | - |
Homo sapiens | ADP + phosphorylated epithelial Na+ channel | - |
? | |
| ATP + epithelial Na+ channel | channel inactivation | Homo sapiens | ADP + phosphorylated epithelial Na+ channel | - |
? | |
| ATP + ezrin | - |
Homo sapiens | ADP + phosphorylated ezrin | - |
? | |
| ATP + ezrin | phosphorylation of ezrin affects the 7TM receptor mediated cytoskeletal reorganization | Homo sapiens | ADP + phosphorylated ezrin | - |
? | |
| ATP + PDEgamma | - |
Homo sapiens | ADP + phosphorylated PDEgamma | - |
? | |
| ATP + PDEgamma | phosphorylation of PDEgamma possibly stimulates EGFR-mediated ERK activation | Homo sapiens | ADP + phosphorylated PDEgamma | - |
? | |
| ATP + PDGFRbeta | - |
Homo sapiens | ADP + phosphorylated PDGFRbeta | - |
? | |
| ATP + phosducin | - |
Homo sapiens | ADP + phosphorylated phosducin | - |
? | |
| ATP + phosducin | phosducin is activated to inhibit Gbetagamma protein | Homo sapiens | ADP + phosphorylated phosducin | - |
? | |
| ATP + ribosomal protein P2 | - |
Homo sapiens | ADP + phosphorylated ribosomal protein P2 | - |
? | |
| ATP + ribosomal protein P2 | activation of P2 | Homo sapiens | ADP + phosphorylated ribosomal protein P2 | - |
? | |
| ATP + synuclein | - |
Homo sapiens | ADP + phosphorylated synuclein | - |
? | |
| ATP + tubulin | - |
Homo sapiens | ADP + phosphorylated tubulin | - |
? | |
| 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 | Homo sapiens | ? | - |
? | |
| additional information | GRK2 binds to and inhibits Galphaq protein via its N-terminal RGS domain, GRK2 interacts with NCS-1 | Homo sapiens | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| beta-adrenergic receptor kinase | - |
Homo sapiens |
| G-protein-coupled receptor kinase 2 | - |
Homo sapiens |
| GRK2 | - |
Homo sapiens |
| More | the enzyme belongs to the G-protein-coupled receptor kinase family | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
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