title: Arrestin-dependent activation of ERK and Src family kinases.
abstract: The four members of the mammalian arrestin family, two visual and two nonvisual, share the property of stimulus-dependent docking to G protein-coupled receptors. This conformational selectivity permits them to function in receptor desensitization, as arrestin binding sterically inhibits G protein coupling. The two nonvisual arrestins further act as adapter proteins, linking receptors to the clathrin-dependent endocytic machinery and regulating receptor sequestration, intracellular trafficking, recycling, and degradation. Arrestins also function as ligand-regulated scaffolds, recruiting catalytically active proteins into receptor-based multiprotein "signalsome" complexes. Arrestin binding thus marks the transition from a transient G protein-coupled state on the plasma membrane to a persistent arrestin-coupled state that continues to signal as the receptor internalizes. Two of the earliest discovered and most studied arrestin-dependent signaling pathways involve regulation of Src family nonreceptor tyrosine kinases and the ERK1/2 mitogen-activated kinase cascade. In each case, arrestin scaffolding imposes constraints on kinase activity that dictate signal duration and substrate specificity. Evidence suggests that arrestin-bound ERK1/2 and Src not only play regulatory roles in receptor desensitization and trafficking but also mediate longer term effects on cell growth, migration, proliferation, and survival.
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors.forename: Erik G
authors.initials: EG
authors.lastname: Strungs
authors.forename: Louis M
authors.initials: LM
authors.lastname: Luttrell
mesh_terms: D019390:Arrestins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008024:Ligands; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D019390:Arrestins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3