Desensitization, Internalization, and Signaling Functions of Beta-arrestins Demonstrated by RNA Interference

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Feb 13

PMID 12582207

Citations 109

Authors

Seungkirl Ahn

Christopher D Nelson

Tiffany Runyan Garrison

William E Miller

Robert J Lefkowitz

Affiliations

Soon will be listed here.

Abstract

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.

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