The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals.

Journal Article (Journal Article;Review)

beta-Arrestins are versatile adapter proteins that form complexes with most G-protein-coupled receptors (GPCRs) following agonist binding and phosphorylation of receptors by G-protein-coupled receptor kinases (GRKs). They play a central role in the interrelated processes of homologous desensitization and GPCR sequestration, which lead to the termination of G protein activation. beta-arrestin binding to GPCRs both uncouples receptors from heterotrimeric G proteins and targets them to clathrin-coated pits for endocytosis. Recent data suggest that beta-arrestins also function as GPCR signal transducers. They can form complexes with several signaling proteins, including Src family tyrosine kinases and components of the ERK1/2 and JNK3 MAP kinase cascades. By recruiting these kinases to agonist-occupied GPCRs, beta-arrestins confer distinct signaling activities upon the receptor. beta-arrestin-Src complexes have been proposed to modulate GPCR endocytosis, to trigger ERK1/2 activation and to mediate neutrophil degranulation. By acting as scaffolds for the ERK1/2 and JNK3 cascades, beta-arrestins both facilitate GPCR-stimulated MAP kinase activation and target active MAP kinases to specific locations within the cell. Thus, their binding to GPCRs might initiate a second wave of signaling and represent a novel mechanism of GPCR signal transduction.

Full Text

Duke Authors

Cited Authors

  • Luttrell, LM; Lefkowitz, RJ

Published Date

  • February 1, 2002

Published In

Volume / Issue

  • 115 / Pt 3

Start / End Page

  • 455 - 465

PubMed ID

  • 11861753

International Standard Serial Number (ISSN)

  • 0021-9533

Digital Object Identifier (DOI)

  • 10.1242/jcs.115.3.455


  • eng

Conference Location

  • England