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

Hirsch, E., Barberis, L., Brancaccio, M., Azzolino, O., Xu, D. Z., Kyriakis, J. M., et al. (2002). Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain. Journal of Cell Biology, 157(3), 481-492.

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Genre: Journal Article
Alternative Title : J. Cell Biol.

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 Creators:
Hirsch, E.1, Author           
Barberis, L., Author
Brancaccio, M., Author
Azzolino, O., Author
Xu, D. Z., Author
Kyriakis, J. M., Author
Silengo, L., Author
Giancotti, F. G., Author
Tarone, G., Author
Fässler, R.2, Author           
Altruda, F., Author
Affiliations:
1External Organizations, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: integrin; cytodomain; RAC; MAPK; proliferation
 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.

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Language(s): eng - English
 Dates: 2002-04-29
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 30254
ISI: 000176427000012
 Degree: -

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Title: Journal of Cell Biology
  Alternative Title : J. Cell Biol.
Source Genre: Journal
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Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 157 (3) Sequence Number: - Start / End Page: 481 - 492 Identifier: ISSN: 0021-9525