Search: onr:"swepub:oai:lup.lub.lu.se:30bd145d-9812-4b4f-bcaa-9c0f42c4a044" >
Defective Rac-media...
Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain
-
Hirsch, E (author)
-
Barberis, L (author)
-
Brancaccio, M (author)
-
show more...
-
Azzolino, O (author)
-
Xu, DZ (author)
-
Kyriakis, JM (author)
-
Silengo, L (author)
-
Giancotti, FG (author)
-
Tarone, G (author)
-
- Fässler, Reinhard (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
-
Altruda, F (author)
-
show less...
-
(creator_code:org_t)
- 2002-04-29
- 2002
- English.
-
In: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 157:3, s. 481-492
- Related links:
-
http://dx.doi.org/10... (free)
-
show more...
-
http://jcb.rupress.o...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- cytodomain
- integrin
- MAPK
- RAC
- proliferation
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database
- By the author/editor
-
Hirsch, E
-
Barberis, L
-
Brancaccio, M
-
Azzolino, O
-
Xu, DZ
-
Kyriakis, JM
-
show more...
-
Silengo, L
-
Giancotti, FG
-
Tarone, G
-
Fässler, Reinhar ...
-
Altruda, F
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cancer and Oncol ...
- Articles in the publication
-
Journal of Cell ...
- By the university
-
Lund University