Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference.

Published

Journal Article

Beta-arrestins bind to activated G protein-coupled receptor kinase-phosphorylated receptors, which leads to their desensitization with respect to G proteins, internalization via clathrin-coated pits, and signaling via a growing list of "scaffolded" pathways. To facilitate the discovery of novel adaptor and signaling roles of beta-arrestins, we have developed and validated a generally applicable interfering RNA approach for selectively suppressing beta-arrestins 1 or 2 expression by up to 95%. Beta-arrestin depletion in HEK293 cells leads to enhanced cAMP generation in response to beta(2)-adrenergic receptor stimulation, markedly reduced beta(2)-adrenergic receptor and angiotensin II receptor internalization and impaired activation of the MAP kinases ERK 1 and 2 by angiotensin II. This approach should allow discovery of novel signaling and regulatory roles for the beta-arrestins in many seven-membrane-spanning receptor systems.

Full Text

Duke Authors

Cited Authors

  • Ahn, S; Nelson, CD; Garrison, TR; Miller, WE; Lefkowitz, RJ

Published Date

  • February 18, 2003

Published In

Volume / Issue

  • 100 / 4

Start / End Page

  • 1740 - 1744

PubMed ID

  • 12582207

Pubmed Central ID

  • 12582207

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.262789099

Language

  • eng

Conference Location

  • United States