Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2.

Journal Article (Journal Article)

beta-Arrestin2 not only plays essential roles in seven membrane-spanning receptor desensitization and internalization but also functions as a signal transducer in mitogen-activated protein kinase cascades. Here we show that the angiotensin II type 1A receptor-mediated activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in HEK-293 cells is increased when the cellular level of beta-arrestin1 is down-regulated by RNA interference but is decreased or eliminated when the cellular level of beta-arrestin2 is diminished. Such reciprocal effects of down-regulated levels of beta-arrestins 1 and 2 are primarily due to differences in the ability of the two forms of beta-arrestins to directly mediate ERK activation. These results are the first to demonstrate reciprocal activity of beta-arrestin isoforms on a signaling pathway and suggest that physiological levels of beta-arrestin1 may act as "dominant-negative" inhibitors of beta-arrestin2-mediated ERK activation.

Full Text

Duke Authors

Cited Authors

  • Ahn, S; Wei, H; Garrison, TR; Lefkowitz, RJ

Published Date

  • February 27, 2004

Published In

Volume / Issue

  • 279 / 9

Start / End Page

  • 7807 - 7811

PubMed ID

  • 14711824

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.C300443200


  • eng

Conference Location

  • United States