G protein coupled receptor kinase

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.

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