G Protein-Coupled Receptor Signaling Through β-Arrestin-Dependent Mechanisms.

Journal Article (Journal Article;Review)

β-arrestin1 (or arrestin2) and β-arrestin2 (or arrestin3) are ubiquitously expressed cytosolic adaptor proteins that were originally discovered for their inhibitory role in G protein-coupled receptor (GPCR) signaling through heterotrimeric G proteins. However, further biochemical characterization revealed that β-arrestins do not just "block" the activated GPCRs, but trigger endocytosis and kinase activation leading to specific signaling pathways that can be localized on endosomes. The signaling pathways initiated by β-arrestins were also found to be independent of G protein activation by GPCRs. The discovery of ligands that blocked G protein activation but promoted β-arrestin binding, or vice-versa, suggested the exciting possibility of selectively activating intracellular signaling pathways. In addition, it is becoming increasingly evident that β-arrestin-dependent signaling is extremely diverse and provokes distinct cellular responses through different GPCRs even when the same effector kinase is involved. In this review, we summarize various signaling pathways mediated by β-arrestins and highlight the physiologic effects of β-arrestin-dependent signaling.

Full Text

Duke Authors

Cited Authors

  • Jean-Charles, P-Y; Kaur, S; Shenoy, SK

Published Date

  • September 2017

Published In

Volume / Issue

  • 70 / 3

Start / End Page

  • 142 - 158

PubMed ID

  • 28328745

Pubmed Central ID

  • PMC5591062

Electronic International Standard Serial Number (EISSN)

  • 1533-4023

Digital Object Identifier (DOI)

  • 10.1097/FJC.0000000000000482


  • eng

Conference Location

  • United States