The Function and Regulation of the G-Protein-Coupled Receptor Kinases

Publisher Summary Signaling by G-protein-coupled receptors (GPCR) can be achieved through receptor phosphorylation and desensitization by the G-protein-coupled receptor kinases (GRKs), a family of serine/threonine kinases, which rapidly phosphorylates agonist-bound receptors and uncouples them from their cognate G protein. There has been an increase in the awareness of the importance of the GRKs in the pathophysiology of disease, particularly ischemic and congestive heart diseases, where changes in the levels and functions of the GRKs have been shown to occur in patients and models of cardiac disease. GPCR mediates the action of a vast array of cellular activators, ranging from the senses of light, taste, and smell, to the circulating hormones and cytokines, and to the complexity of neurotransmitters within the synapse. The uncoupling of the receptor from its G protein has been explained in detail. Here the receptor undergoes phosphorylation either heterologously, in a nonagonist-dependent manner, by the second-messenger-dependent protein kinases, or homologously by the agonist dependent receptor specific G-protein-coupled receptor kinases. The possibility that the GRKs may be involved in the pathogenesis of disease states, or that they are potential targets for therapeutic intervention, offers many possibilities for new avenues of research.