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]
Identifiers
EC number 2.7.11.16
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
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]

References[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]