Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E05-12-1104 on June 7, 2006

Vol. 17, Issue 8, 3591-3597, August 2006

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
E05-12-1104v1
17/8/3591    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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zarich, N.
Right arrow Articles by Rojas, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zarich, N.
Right arrow Articles by Rojas, J. M.

Grb2 Is a Negative Modulator of the Intrinsic Ras-GEF Activity of hSos1Formula

Natasha Zarich, José Luis Oliva, Natalia Martínez, Rocío Jorge, Alicia Ballester, Silvia Gutiérrez-Eisman, Susana García-Vargas, and José M. Rojas

Unidad de Biología Celular, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain

Submitted December 6, 2005; Revised May 10, 2005; Accepted May 31, 2006
Monitoring Editor: J. Silvio Gutkind

hSos1 is a Ras guanine-nucleotide exchange factor. It was suggested that the carboxyl-terminal region of hSos1 down-regulates hSos1 functionality and that the intrinsic guanine-nucleotide exchange activity of this protein may be different before and after stimulation of tyrosine kinase receptors. Using different myristoylated hSos1 full-length and carboxyl-terminal truncated mutants, we show that Grb2 function accounts not only for recruitment of hSos1 to the plasma membrane but also for modulation of hSos1 activity. Our results demonstrate that the first two canonical Grb2 binding sites, inside the carboxyl-terminal region of hSos1, are responsible for this regulation. Following different approaches, such as displacement of Grb2 from the hSos1-Grb2 complex or depletion of Grb2 levels by small interfering RNA, we found that the full-length Grb2 proteins mediate negative regulation of the intrinsic Ras guanine-nucleotide exchange activity of hSos1.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05-12-1104) on June 7, 2006.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: José M. Rojas ( jmrojas{at}isciii.es)




This article has been cited by other articles:


Home page
 RNAHome page
J. Moses, A. Goodchild, and L. P. Rivory
Intended transcriptional silencing with siRNA results in gene repression through sequence-specific off-targeting
RNA, February 1, 2010; 16(2): 430 - 441.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2006 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.