THE ROLE OF RECEPTOR KINASES AND ARRESTINS IN G-PROTEIN-COUPLED RECEPTOR REGULATION

G protein-coupled receptors (GPRs) play a key role in controlling horm onal regulation of numerous second-messenger pathways. However, follow ing agonist activation, most GPRs rapidly lose their ability to respon d to hormone. For many GPRs, this process, commonly referred to as des ensitization, appears to be primarily mediated by two protein families : G protein-coupled receptor kinases (GRKs) and arrestins. GRKs specif ically bind to the agonist-occupied receptor, thereby promoting recept or phosphorylation, which in turn leads to arrestin binding. Arrestin binding precludes receptor/G protein interaction leading to functional desensitization. Many GPRs are then removed from the plasma membrane via clathrin-mediated endocytosis. Recent studies have implicated endo cytosis in the resensitization of GPRs and have linked both GRKs and a rrestins to this process. In this review, we discuss the role of GRKs and arrestins in regulating agonist-specific signaling and trafficking of GPRs.