title: Arrestins as regulators of kinases and phosphatases.
abstract: The discovery that, in addition to mediating G protein-coupled receptor (GPCR) desensitization and endocytosis, arrestins bind to diverse catalytically active nonreceptor proteins and act as ligand-regulated signaling scaffolds led to a paradigm shift in the study of GPCR signal transduction. Research over the past decade has solidified the concept that arrestins confer novel GPCR-signaling capacity by recruiting protein and lipid kinase, phosphatase, phosphodiesterase, and ubiquitin ligase activity into receptor-based multiprotein "signalsome" complexes. Signalsomes regulate downstream pathways controlled by Src family nonreceptor tyrosine kinases, mitogen-activated protein kinases, protein kinase B (AKT), glycogen synthase kinase 3, protein phosphatase 2A, nuclear factor-κB, and several others, imposing spatial and temporal control on their function. While many arrestin-bound kinases and phosphatases are involved in the control of cytoskeletal rearrangement, vesicle endocytosis, exocytosis, and cell migration, other signals reach into the nucleus, affecting cell proliferation, apoptosis, and survival. Indeed, the kinase/phosphatase network regulated by arrestins may be fully as diverse as that regulated by heterotrimeric G proteins.
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Luttrell
authors.forename: William E
authors.initials: WE
authors.lastname: Miller
mesh_terms: D019390:Arrestins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019390:Arrestins; D043562:Receptors, G-Protein-Coupled; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases