JCB logo
R&D Systems
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 6 March 2006. doi:10.1083/jcb.200506001
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 6, 817-822
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Khanday, F. A.
Right arrow Articles by Irani, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Khanday, F. A.
Right arrow Articles by Irani, K.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Report

 Sos-mediated activation of rac1 by p66shc

Firdous A. Khanday1, Lakshmi Santhanam2, Kenji Kasuno1, Tohru Yamamori1, Asma Naqvi1, Jeremy DeRicco1, Artem Bugayenko2, Ilwola Mattagajasingh1, Andrea Disanza3, Giorgio Scita3, and Kaikobad Irani1

1 Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213
2 The Johns Hopkins University, Baltimore, MD 21205
3 Instituto Fondazione Italiana Ricerca sul Cancro di Oncologia Molecolare, 20139 Milan, Italy

Correspondence to Kaikobad Irani: iranik{at}upmc.edu


Abstract
The Son of Sevenless 1 protein (sos1) is a guanine nucleotide exchange factor (GEF) for either the ras or rac1 GTPase. We show that p66shc, an adaptor protein that promotes oxidative stress, increases the rac1-specific GEF activity of sos1, resulting in rac1 activation. P66shc decreases sos1 bound to the growth factor receptor bound protein (grb2) and increases the formation of the sos1–eps8–e3b1 tricomplex. The NH2-terminal proline-rich collagen homology 2 (CH2) domain of p66shc associates with full-length grb2 in vitro via the COOH-terminal src homology 3 (C-SH3) domain of grb2. A proline-rich motif (PPLP) in the CH2 domain mediates this association. The CH2 domain competes with the proline-rich COOH-terminal region of sos1 for the C-SH3 domain of grb2. P66shc-induced dissociation of sos1 from grb2, formation of the sos1–eps8–e3b1 complex, rac1-specific GEF activity of sos1, rac1 activation, and oxidative stress are also mediated by the PPLP motif in the CH2 domain. This relationship between p66shc, grb2, and sos1 provides a novel mechanism for the activation of rac1.

Abbreviations used in this paper: CH, collagen homology; C-SH3, COOH-terminal SH3; C-sos1, COOH-terminal region of sos1; GEF, guanine nucleotide exchange factor; HEK, human embryonic kidney; MEF, mouse embryonic fibroblast; N-SH3, NH2-terminal SH3; ROS, reactive oxygen species; RTK, receptor tyrosine kinase; SH, src homology.


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


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents