MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Other Versions of this Article:
MCB.01917-07v1
28/9/2851    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Hao, Y.
Right arrow Articles by Feig, L. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hao, Y.
Right arrow Articles by Feig, L. A.

Next Article 

Molecular and Cellular Biology, May 2008, p. 2851-2859, Vol. 28, No. 9
0270-7306/08/$08.00+0     doi:10.1128/MCB.01917-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

RalGDS Couples Growth Factor Signaling to Akt Activation{triangledown}

Yansheng Hao, Richard Wong, and Larry A. Feig*

Sackler School of Graduate Biomedical Sciences and Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111

Received 24 October 2007/ Returned for modification 23 November 2007/ Accepted 10 February 2008

The Akt kinase is a key regulator of cell proliferation and survival. It is activated in part by PDK1-induced phosphorylation. Here we show that RalGDS, a Ras effector protein that activates Ral GTPases, has a second function that promotes Akt phosphorylation by PDK1 by bringing these two kinases together. In support of this conclusion is our finding that suppression of RalGDS expression in cells inhibits both epidermal growth factor and insulin-induced phosphorylation of Akt. Moreover, while PDK1 complexes with N-GDS, Akt complexes with the central region of RalGDS through an intermediary, JIP1. The biological significance of this newly discovered RalGDS function is highlighted by the observation that an N-terminally deleted mutant of RalGDS that retains the ability to activate Ral proteins but loses the ability to activate Akt also fails to promote cell proliferation. Thus, RalGDS forms a nexus that transduces growth factor signaling to both Ral GTPase and Akt-mediated signaling cascades.

* Corresponding author. Mailing address: Sackler School of Graduate Biomedical Sciences and Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111. Phone: (617) 636-6956. Fax: (617) 636-6409. E-mail: larry.feig{at}tufts.edu

{triangledown} Published ahead of print on 19 February 2008.

Molecular and Cellular Biology, May 2008, p. 2851-2859, Vol. 28, No. 9
0270-7306/08/$08.00+0     doi:10.1128/MCB.01917-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2008 by the American Society for Microbiology. All rights reserved.