GRK

G protein-coupled receptor kinases, GRK1 through GRK7, are the dedicated negative regulators of GPCR signaling. They phosphorylate serines and threonines on agonist-occupied receptors, which recruits beta-arrestins, uncouples the receptor from its G protein, and initiates internalization and desensitization. The GRK2/GRK3 subfamily (formerly beta-ARK1/2) contains an N-terminal RGS-homology domain, the central kinase domain, and a C-terminal PH domain that binds Gbeta-gamma to deliver the kinase to activated receptors at the membrane, whereas GRK4, GRK5, and GRK6 are membrane-associated by lipid modification. GRK1 in photoreceptors phosphorylates light-activated rhodopsin, and its defects underlie Oguchi disease. Elevated GRK2 levels accompany heart failure and hypertension, and recombinant GRKs are standard tools for desensitization assays and GPCR drug screening.