Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization

A.P. Gilmore, Anthony Metcalfe, L.M. Romer, C.H. Streuli

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
JournalJournal of Cell Biology
Volume149
Issue number2
DOIs
Publication statusPublished - 17 Apr 2000

Bibliographical note

© 2000 The Rockefeller University Press

Keywords

  • apoptosis
  • Bax
  • mammary
  • adhesion
  • pp125FAK

Fingerprint Dive into the research topics of 'Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization'. Together they form a unique fingerprint.

Cite this