JCB logo
Quantitative Colocalization Analysis Software
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 3 January 2002. doi:10.1083/jcb.200108035
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 582K)
Right arrow PPT slides of all figures
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 Innocenti, M.
Right arrow Articles by Scita, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Innocenti, M.
Right arrow Articles by Scita, G.
Right arrowPubmed/NCBI databases
*Substance via MeSH
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?

© The Rockefeller University Press, 0021-9525/2002/1/125 $5.00
The Journal of Cell Biology, Volume 156, Number 1, January 7, 2002 125-136

Article

Mechanisms through which Sos-1 coordinates the activation of Ras and Rac



Metello Innocenti1, Pierluigi Tenca1, Emanuela Frittoli1, Mario Faretta1, Arianna Tocchetti1, Pier Paolo Di Fiore1,2,3 and Giorgio Scita1

1 Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy
2 IFOM, The FIRC Institute for Molecular Oncology, 20134 Milan, Italy
3 Dipartimento di Medicina Chirurgia ed Odontoiatria, Universita' degli Studi di Milano, 20122 Milan, Italy

Address correspondence to Giorgio Scita, Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti, 435, 20141 Milano, Italy. Tel.: 39-0257489825. Fax: 39-0257489851. E-mail: gscita{at}ieo.it

Signaling from receptor tyrosine kinases (RTKs)* requires the sequential activation of the small GTPases Ras and Rac. Son of sevenless (Sos-1), a bifunctional guanine nucleotide exchange factor (GEF), activates Ras in vivo and displays Rac-GEF activity in vitro, when engaged in a tricomplex with Eps8 and E3b1–Abi-1, a RTK substrate and an adaptor protein, respectively. A mechanistic understanding of how Sos-1 coordinates Ras and Rac activity is, however, still missing. Here, we demonstrate that (a) Sos-1, E3b1, and Eps8 assemble into a tricomplex in vivo under physiological conditions; (b) Grb2 and E3b1 bind through their SH3 domains to the same binding site on Sos-1, thus determining the formation of either a Sos-1–Grb2 (S/G) or a Sos-1–E3b1–Eps8 (S/E/E8) complex, endowed with Ras- and Rac-specific GEF activities, respectively; (c) the Sos-1–Grb2 complex is disrupted upon RTKs activation, whereas the S/E/E8 complex is not; and (d) in keeping with the previous result, the activation of Ras by growth factors is short-lived, whereas the activation of Rac is sustained. Thus, the involvement of Sos-1 at two distinct and differentially regulated steps of the signaling cascade allows for coordinated activation of Ras and Rac and different duration of their signaling within the cell.

Key Words: Sos-1; Eps8; E3b1; Ras; Rac


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