Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain

Research output: Contribution to journalArticle

Abstract

Cell matrix adhesion is required for cell proliferation and survival. Here we report that mutation by gene targeting of the cytoplasmic tail of beta(1) integrin leads to defective proliferation and survival both in vivo and in vitro. Primary murine embryonic fibroblasts (MEFs) derived from mutant homozygotes display defective cell cycle coupled to impaired activation of the FAK-P13K-Akt and Rac-JNK signaling pathways. Expression in homozygous MEFs of a constitutively active form of Rac is able to rescue proliferation, survival, and JNK activation. Moreover, although showing normal Erk phosphorylation, mutant cells fail to display Erk nuclear translocation upon fibronectin adhesion. However, expression of the constitutively activated form of Rac restores Erk nuclear localization, suggesting that adhesion-dependent Rac activation is necessary to integrate signals directed to promote MAPK activity. Altogether, our data provide the evidence for an epistatic interaction between the beta(1) integrin cytoplasmic domain and Rac, and indicate that this anchorage-dependent signaling pathway is crucial for cell growth control.

Details

Authors
  • E Hirsch
  • L Barberis
  • M Brancaccio
  • O Azzolino
  • DZ Xu
  • JM Kyriakis
  • L Silengo
  • FG Giancotti
  • G Tarone
  • Reinhard Fässler
  • F Altruda
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • cytodomain, integrin, MAPK, RAC, proliferation
Original languageEnglish
Pages (from-to)481-492
JournalJournal of Cell Biology
Volume157
Issue number3
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Pathology (013031100), Pathology, (Lund) (013030000)