G protein-coupled receptor kinase

G protein-coupled receptor kinase

Crystal structure of G protein coupled receptor kinase 1 (GRK1) bound to ATP.[1]
EC number
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

G protein-coupled receptor kinases (GRKs, GPCRKs) are a family of protein kinases that regulate the activity of G protein-coupled receptors (GPCRs) by phosphorylating their intracellular domains after their associated G proteins have been released and activated.

The phosphorylated serine and threonine residues act as binding sites for arrestin proteins that prevent the reassociation of the G proteins with their receptors, thereby preventing reactivation of the signaling pathway.

GRKs regulate also cellular responses independent of their kinase activity. In particular, G protein-coupled receptor kinase 2 interacts with a diverse repertoire of non-GPCR substrates.[2]

GRK1 is involved with Rhodopsin phosphorlylation and deactivation. Defects in GRK1 result in Oguchi disease 2.[3]

Types of GRKs

Name Notes Gene OMIM
G protein-coupled receptor kinase 1 Rhodopsin kinase GRK1 180381
G protein-coupled receptor kinase 2 β-Adrenergic receptor kinase 1 (BARK1) GRK2 109635
G protein-coupled receptor kinase 3 β-Adrenergic receptor kinase 2 (BARK2) GRK3 109636
G protein-coupled receptor kinase 4 Has been associated with regulation of kidney tubule function GRK4 137026
G protein-coupled receptor kinase 5 Knockout mice have altered core body temperature GRK5 600870
G protein-coupled receptor kinase 6 Knockout mice are supersensitive to dopaminergics[4] GRK6 600869
G protein-coupled receptor kinase 7 Cone opsin kinase GRK7 606987

See also


  1. PDB: 3C4W; Singh P, Wang B, Maeda T, Palczewski K, Tesmer JJ (May 2008). "Structures of rhodopsin kinase in different ligand states reveal key elements involved in G protein-coupled receptor kinase activation". J. Biol. Chem. 283 (20): 14053–62. doi:10.1074/jbc.M708974200. PMC 2376226Freely accessible. PMID 18339619.
  2. Evron T, Daigle TL, Caron MG (March 2012). "GRK2: multiple roles beyond G protein-coupled receptor desensitization". Trends Pharmacol. Sci. 33 (3): 154–64. doi:10.1016/j.tips.2011.12.003. PMC 3294176Freely accessible. PMID 22277298..
  3. "GRK1 G protein-coupled receptor kinase 1 [ Homo sapiens ]". National Center for Biotechnology Information. Retrieved 14 April 2011.
  4. Gainetdinov RR, Bohn LM, Sotnikova TD, et al. (April 2003). "Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice". Neuron. 38 (2): 291–303. doi:10.1016/S0896-6273(03)00192-2. PMID 12718862. Retrieved 2009-08-14.

Further reading

  • Sobierajska K, Fabczak H, Fabczak S (2005). "Mechanisms of Regulation and Function of G Protein-Coupled Receptor Kinases]". Postepy Biochemii (in Polish). 51 (4): 421–9. PMID 16676577. 
  • Ribas C, Penela P, Murga C, Salcedo A, García-Hoz C, Jurado-Pueyo M, Aymerich I, Mayor F (April 2007). "The G protein-coupled receptor kinase (GRK) interactome: role of GRKs in GPCR regulation and signaling". Biochimica et Biophysica Acta. 1768 (4): 913–22. doi:10.1016/j.bbamem.2006.09.019. PMID 17084806. 
  • Ma L, Gao J, Chen X (2005). "G Protein-Coupled Receptor Kinases". In Devi LA. The G Protein-Coupled Receptors Handbook (Contemporary Clinical Neuroscience). Totowa, NJ: Humana Press. ISBN 1-58829-365-3. 
  • Kurose H (2000). "G Protein-Coupled Kinases and Desensitization of Receptors". In Bernstein G, Tatsuya H. G protein-coupled receptors. Boca Raton: CRC Press. ISBN 0-8493-3384-9. 

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