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Role of kinase-independent and -dependent functions of FAK in endothelial cell survival and barrier function during embryonic development.

Authors :
Zhao, Xiaofeng
Xu Peng
Sun, Shaogang
Park, Ann Y. J.
Guan, Jun-Lin
Source :
Journal of Cell Biology. 6/14/2010, Vol. 189 Issue 6, p955-965. 11p.
Publication Year :
2010

Abstract

Focal adhesion kinase (FAK) is essential for vascular development as endothelial cell (EC)-specific knockout of FAK (conditional FAK knockout [CFKO] mice) leads to embryonic lethality. In this study, we report the differential kinase-independent and -dependent functions of FAK in vascular development by creating and analyzing an EC-specific FAK kinase-defective (KD) mutant knockin (conditional FAK knockin [CFKI]) mouse model. CFKI embryos showed apparently normal development through embryonic day (E) 13.5, whereas the majority of CFKO embryos died at the same stage. Expression of KD FAK reversed increased EC apoptosis observed with FAK deletion in embryos and in vitro through suppression of up-regulated p21. However, vessel dilation and defective angiogenesis of CFKO embryos were not rescued in CFKI embryos. ECs without FAK or expressing KD FAK showed increased permeability, abnormal distribution of vascular endothelial cadherin (VE-cadherin), and reduced VE-cadherin Y658 phosphorylation. Together, our data suggest that kinase-independent functions of FAK can support EC survival in vascular development through E13.5 but are insufficient for maintaining EC function to allow for completion of embryogenesis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219525
Volume :
189
Issue :
6
Database :
Academic Search Index
Journal :
Journal of Cell Biology
Publication Type :
Academic Journal
Accession number :
52517988
Full Text :
https://doi.org/10.1083/jcb.200912094