HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 16, 10611-10620, April 18, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/16/10611    most recent M710515200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by DeWire, S. M. Articles by Lefkowitz, R. J. PubMed PubMed Citation Articles by DeWire, S. M. Articles by Lefkowitz, R. J. Social Bookmarking                      What's this?

β-Arrestin-mediated Signaling Regulates Protein Synthesis^*

Scott M. DeWire¹, Jihee Kim, Erin J. Whalen, Seungkirl Ahn, Minyong Chen, and Robert J. Lefkowitz, An Investigator with the Howard Hughes Medical Institute^¶2

From the Departments of Medicine and ^¶Biochemistry and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710

Seven transmembrane receptors (7TMRs) exert strong regulatory influences on virtually all physiological processes. Although it is historically assumed that heterotrimeric G proteins mediate these actions, there is a newer appreciation that β-arrestins, originally thought only to desensitize G protein signaling, also serve as independent receptor signal transducers. Recently, we found that activation of ERK1/2 by the angiotensin receptor occurs via both of these distinct pathways. In this work, we explore the physiological consequences of β-arrestin ERK1/2 signaling and delineate a pathway that regulates mRNA translation and protein synthesis via Mnk1, a protein that both physically interacts with and is activated by β-arrestins. We show that β-arrestin-dependent activation of ERK1/2, Mnk1, and eIF4E are responsible for increasing translation rates in both human embryonic kidney 293 and rat vascular smooth muscle cells. This novel demonstration that β-arrestins regulate protein synthesis reveals that the spectrum of β-arrestin-mediated signaling events is broader than previously imagined.

Received for publication, December 26, 2007 , and in revised form, February 6, 2008.

^* This work was supported in part by National Institutes of Health Grants HL16037 and HL70631. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

¹ Supported by a grant from the Howard Hughes Medical Institute.

² To whom correspondence should be addressed: Box 3821, Duke University Medical Center, Durham, NC 27710. E-mail: lefko001{at}receptor-biol.duke.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?