Molecular Biology of the Cell track citations

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


     

MBC in Press, published online ahead of print January 26, 2003
Mol. Biol. Cell 10.1091/mbc.E02-06-0352

A more recent version of this article appeared on April 1, 2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E02-06-0352v1
14/4/1691    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 Maroun, C. R.
Right arrow Articles by Park, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maroun, C. R.
Right arrow Articles by Park, M.

Submitted on June 20, 2002
Revised on November 29, 2002
Accepted on December 9, 2002

Membrane-targeting of the Gab1 scaffolding protein through the Src myristoylation sequence substitutes for the Gab1 PH domain and switches an EGF response to an invasive morphogenic program

Christiane R. Maroun1, Monica A. Naujokas1, and Morag Park2*

1 Department of Medicine, Molecular Oncology Group, McGill University Health Centre, McGill University, Montreal, Quebec, H3A 1A1, Canada
2 Departments of Medicine, Biochemistry and Oncology, Molecular Oncology Group, McGill University Health Centre, McGill University, Montreal, Quebec, H3A 1A1, Canada

* Corresponding author. E-mail address: morag{at}molonc.mcgill.ca.

The hepatocyte growth factor receptor tyrosine kinase, Met, promotes cell dissociation and the inherent morphogenic program of epithelial cells. In a search for substrates downstream from Met, we have previously identified the Grb2-associated binder-1 (Gab1) as critical for the morphogenic program. Gab1 is a scaffold protein that acts to diversify the signal downstream from the Met receptor through its ability to couple with multiple signal transduction pathways. Gab1 contains a pleckstrin homology (PH) domain with specificity for phosphatidylinositol 3,4,5-trisphosphate. The phospholipid binding capacity of the Gab1 PH domain is required for the localiation of Gab1 at sites of cell-cell contact in colonies of epithelial cells and for epithelial morphogenesis, suggesting that PH domain dependent subcellular localization of Gab1 is a prerequisite for function. We have investigated the requirement for membrane localization of Gab1 for biological activity. We show that substitution of the Gab1 PH domain with the myristoylation signal from the c-Src protein is sufficient to replace the Gab1 PH domain for epithelial morphogenesis. The membrane targeting of Gab1, enhances Rac activity in the absence of stimulation and switches a non-morphogenic non-invasive response to EGF to a morphogenic invasive program. These results sugest that the subcellular localization of Gab1 is a critical determinant for epithelial morphogenesis and invasiveness.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
P. Timpson, A. S. Wilson, G. M. Lehrbach, R. L. Sutherland, E. A. Musgrove, and R. J. Daly
Aberrant Expression of Cortactin in Head and Neck Squamous Cell Carcinoma Cells Is Associated with Enhanced Cell Proliferation and Resistance to the Epidermal Growth Factor Receptor Inhibitor Gefitinib
Cancer Res., October 1, 2007; 67(19): 9304 - 9314.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2003 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.