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          Institute: MPI für Biochemie     Collection: Molecular Medicine (R. Fässler)     Display Documents



ID: 30254.0, MPI für Biochemie / Molecular Medicine (R. Fässler)
Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain
Authors:Hirsch, E.; Barberis, L.; Brancaccio, M.; Azzolino, O.; Xu, D. Z.; Kyriakis, J. M.; Silengo, L.; Giancotti, F. G.; Tarone, G.; Fässler, R.; Altruda, F.
Language:English
Date of Publication (YYYY-MM-DD):2002-04-29
Title of Journal:Journal of Cell Biology
Journal Abbrev.:J. Cell Biol.
Volume:157
Issue / Number:3
Start Page:481
End Page:492
Review Status:Peer-review
Audience:Not Specified
Abstract / Description: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.
Free Keywords:integrin; cytodomain; RAC; MAPK; proliferation
Comment of the Author/Creator:Date: 2002, APR 29
External Publication Status:published
Document Type:Article
Communicated by:N.N.
Affiliations:MPI für Biochemie/Molecular Medicine (R. Fässler)
External Affiliations:Univ Turin, Dipartimento Genet Biol & Biochim, Via Santena 5,; I-10126 Turin, Italy; Univ Turin, Dipartimento Genet Biol & Biochim, I-10126 Turin, Italy; San Giovanni Battista Hosp, Expt Med Res Ctr, I-10126 Turin, Italy; Univ Lund Hosp, Dept Expt Pathol, S-22285 Lund, Sweden; Massachusetts Gen Hosp, Med Serv, Diabet Res Lab, Boston, MA 02129 USA; Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA
Identifiers:ISI:000176427000012 [ID No:1]
ISSN:0021-9525 [ID No:2]
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