G-PROTEIN-COUPLED RECEPTOR KINASES

G protein-coupled receptor kinases (GRKs) constitute a family of six m ammalian serine/threonine protein kinases that phosphorylate agonist-b ound, or activated, G protein-coupled receptors (GPCRs) as their prima ry substrates. GRK-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling, or desensitization. This r eview focuses on the regulation of GRK activity by a variety of allost eric and other factors: agonist-stimulated GPCRs, beta gamma subunits of heterotrimeric GTP-binding proteins, phospholipid cofactors, the ca lcium-binding proteins calmodulin and recovering posttranslational iso prenylation and palmitoylation, autophosphorylation, and protein kinas e C-mediated GRK phosphorylation. Studies employing recombinant, purif ied proteins, cell culture, and transgenic animal models attest to the general importance of GRKs in regulating a vast array of GPCRs both i n vitro and in vivo.