G Protein-Coupled Receptor Signaling Through β-Arrestin-Dependent Mechanisms.
Published
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
- 28328745
Electronic International Standard Serial Number (EISSN)
- 1533-4023
Digital Object Identifier (DOI)
- 10.1097/FJC.0000000000000482
Language
- eng
Conference Location
- United States