G protein-coupled receptor kinase

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G protein-coupled receptor kinase
Gprotein-coupled receptor kinase.png
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. In other words, these proteins are the mediators of tolerance related to GPCRs via up- and downregulation.

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[edit]

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) ADRBK1 (GRK2) 109635
G protein-coupled receptor kinase 3 β-Adrenergic receptor kinase 2 (BARK2) ADRBK2 (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[edit]


  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 2376226. 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 3294176. 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[edit]