title: Classical and new roles of beta-arrestins in the regulation of G-protein-coupled receptors.
abstract: In the classical model of G-protein-coupled receptor (GPCR) regulation, arrestins terminate receptor signalling. After receptor activation, arrestins desensitize phosphorylated GPCRs, blocking further activation and initiating receptor internalization. This function of arrestins is exemplified by studies on the role of arrestins in the development of tolerance to, but not dependence on, morphine. Arrestins also link GPCRs to several signalling pathways, including activation of the non-receptor tyrosine kinase SRC and mitogen-activated protein kinase. In these cascades, arrestins function as adaptors and scaffolds, bringing sequentially acting kinases into proximity with each other and the receptor. The signalling roles of arrestins have been expanded even further with the discovery that the formation of stable receptor-arrestin complexes initiates photoreceptor apoptosis in Drosophila, leading to retinal degeneration. Here we review our current understanding of arrestin function, discussing both its classical and newly discovered roles.
authors.affiliation: The Howard Hughes Medical Institute and the Departments of Medicine and Biochemistry, Box 3821, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Pierce
authors.forename: R J
authors.initials: RJ
authors.lastname: Lefkowitz
mesh_terms: D000818:Animals; D019390:Arrestins / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000502:physiology*
chemical_list: D019390:Arrestins; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins