JCB logo
R&D Systems: New Poster Available
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1015K)
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 CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gilmore, A. P.
Right arrow Articles by Streuli, C. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gilmore, A. P.
Right arrow Articles by Streuli, C. H.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/2000//431 $5.00
The Journal of Cell Biology, Volume 149, Number 2, , 2000 431-446

Original Article

Integrin-Mediated Survival Signals Regulate the Apoptotic Function of Bax through Its Conformation and Subcellular Localization



Andrew P. Gilmorea, Anthony D. Metcalfea, Lewis H. Romerb, and Charles H. Streulia

a School of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK
b Departments of Cell Biology and Anatomy, Pediatrics, and Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
School of Biological Sciences, University of Manchester, 3.239 Stopford Building, Oxford Road, Manchester M13 9PT, UK.+44 161 275 7700+44 161 275 5576

cstreuli{at}man.ac.uk

Most normal cells require adhesion to extracellular matrix for survival, but the molecular mechanisms that link cell surface adhesion events to the intracellular apoptotic machinery are not understood. Bcl-2 family proteins regulate apoptosis induced by a variety of cellular insults through acting on internal membranes. A pro-apoptotic Bcl-2 family protein, Bax, is largely present in the cytosol of many cells, but redistributes to mitochondria after treatment with apoptosis-inducing drugs. Using mammary epithelial cells as a model for adhesion-regulated survival, we show that detachment from extracellular matrix induced a rapid translocation of Bax to mitochondria concurrent with a conformational change resulting in the exposure of its BH3 domain. Bax translocation and BH3 epitope exposure were reversible and occurred before caspase activation and apoptosis. Pp125FAK regulated the conformation of the Bax BH3 epitope, and PI 3-kinase and pp60src prevented apoptosis induced by defective pp125FAK signaling. Our results provide a mechanistic connection between integrin-mediated adhesion and apoptosis, through the kinase-regulated subcellular distribution of Bax.

Key Words: apoptosis • Bax • mammary • adhesion • pp125FAK

© 2000 The Rockefeller University Press

Abbreviations used in this paper: BH, Bcl-2 homology; BrdU, bromodeoxyuridine; DN-FAK, dominant-negative FAK; DSS, disuccinimidyl suberate; ECM, extracellular matrix; PI 3-kinase, phosphatidylinositol 3-kinase; pp125FAK, focal adhesion kinase; polyHEMA, polyhydroxyethylmethacrylate.


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related Article


J. Cell Biol. 2000 149: 1-2. [Full Text] [PDF]





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