G Protein-Coupled Receptor Kinases

Abstract

As the largest family of membrane receptors, G protein-coupled receptors (GPCRs) transduce a large number of extracellular signals from hormones, neurotransmitters, chemokines, and other environmental stimuli to the interior of cells and play fundamental roles in the regulation of cellular functions. One of the most important features of GPCR-mediated signal transduction is that the activation of the receptor also triggers a feedback regulatory mechanism to attenuate GPCR-mediated signal transduction (homologous desensitization) in the cell. Homologous receptor desensitization is a common mechanism employed by the cell to prevent potential harmful effects that result from persistent activation of the signaling pathways. The initial event of GPCR desensitization occurs within seconds to minutes after agonist binding and is induced by receptor phosphorylation that is catalyzed by GPCR kinases (GRKs) (1).