G protein-coupled receptor kinase

G protein-coupled receptor kinase
Crystal structure of G protein coupled receptor kinase 1 (GRK1) bound to ATP.
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
Search PMC articles PubMed articles

G protein-coupled receptor kinases (GRKs, GPCRKs) are a family of protein kinases which 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 which prevent the reassociation of the G proteins with their receptors, thereby preventing reactivation of the signaling pathway.

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

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)	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	GRK6	600869
G protein-coupled receptor kinase 7	Cone opsin kinase	GRK7	606987

See also

• Downregulation and upregulation
• G protein-coupled receptor
• Phosphorylation
• Protein kinase

Further reading

• Sobierajska K, Fabczak H, Fabczak S (2005). "Mechanisms of Regulation and Function of G Protein-Coupled Receptor Kinases]" (in Polish). Postepy Biochemii 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. http://books.google.com/books?id=sW2SY9zzydMC&pg=PA149. 
• 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. http://books.google.com/books?id=jtSqgZXIVt4C&pg=PA186.