Defective Rac-mediated proliferation and survival after targeted mutation of the β1 integrin cytodomain Journal Article
| Authors: | Hirsch, E.; Barberis, L.; Brancaccio, M.; Azzolino, O.; Xu, D.; Kyriakis, J. M.; Silengo, L.; Giancotti, F. G.; Tarone, G.; Fässler, R.; Altruda, F. |
| Article Title: | Defective Rac-mediated proliferation and survival after targeted mutation of the β1 integrin cytodomain |
| Abstract: | Cell matrix adhesion is required for cell proliferation and survival. Here we report that mutation by gene targeting of the cytoplasmic tail of β1 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-PI3K-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 β1 integrin cytoplasmic domain and Rac, and indicate that this anchorage-dependent signaling pathway is crucial for cell growth control. |
| Keywords: | signal transduction; mitogen activated protein kinase; gene mutation; mutation; nonhuman; protein localization; cell proliferation; animal cell; mouse; animals; mice; cell survival; gene targeting; cell cycle; cell division; cell growth; alleles; enzyme activity; phosphorylation; animalia; 1-phosphatidylinositol 3-kinase; growth regulation; homozygote; murinae; fibroblast; fibroblasts; mitogen activated protein kinase 1; protein structure, tertiary; proliferation; mitogen-activated protein kinases; cell adhesion; integrin; protein isoforms; mapk; rac protein; fibronectin; rac gtp-binding proteins; rac; beta1 integrin; antigens, cd29; priority journal; article; fetal death; cytodomain |
| Journal Title: | Journal of Cell Biology |
| Volume: | 157 |
| Issue: | 3 |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2002-04-29 |
| Start Page: | 481 |
| End Page: | 492 |
| Language: | English |
| DOI: | 10.1083/jcb.200111065 |
| PUBMED: | 11980921 |
| PROVIDER: | scopus |
| PMCID: | PMC2173276 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
