Induced focal adhesion kinase expression suppresses apoptosis by activating NF-kappaB signaling in intestinal epithelial cells

Focal adhesion kinase (FAK) integrates various extracellular and intracellular signals and is implicated in a variety of biological functions, but its exact role and downstream targeting signals in the regulation of apoptosis in intestinal epithelial cells (IECs) remains unclear. The current study t...

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Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2006-05, Vol.59 (5), p.C1310
Main Authors: Zhang, Huifang M, Keledjian, Kaspar M, Rao, Jaladanki N, Zou, Tongtong
Format: Article
Language:English
Subjects:
Cell adhesion & migration
Enzymes
Gene expression
Signal transduction
Online Access:Get full text
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Summary:Focal adhesion kinase (FAK) integrates various extracellular and intracellular signals and is implicated in a variety of biological functions, but its exact role and downstream targeting signals in the regulation of apoptosis in intestinal epithelial cells (IECs) remains unclear. The current study tested the hypothesis that FAK has an antiapoptotic role in the IEC-6 cell line by altering NF-{kappa}B signaling. Induced FAK expression by stable transfection with the wild-type (WT)-FAK gene increased FAK phosphorylation, which was associated with an increase in NF-{kappa}B activity. These stable WT-FAK-transfected IECs also exhibited increased resistance to apoptosis when they were exposed to TNF-{alpha} plus cycloheximide (TNF-{alpha}/CHX). Specific inhibition of NF-{kappa}B by the recombinant adenoviral vector containing the I{kappa}B{alpha} superrepressor prevented increased resistance to apoptosis in WT-FAK-transfected cells. In contrast, inactivation of FAK by ectopic expression of dominant-negative mutant of FAK (DNM-FAK) inhibited NF-{kappa}B activity and increased the sensitivity to TNF-{alpha}/CHX-induced apoptosis. Furthermore, induced expression of endogenous FAK by depletion of cellular polyamines increased NF-{kappa}B activity and resulted in increased resistance to TNF-{alpha}/CHX-induced apoptosis, both of which were prevented by overexpression of DNM-FAK. These results indicate that increased expression of FAK suppresses TNF-{alpha}/CHX-induced apoptosis, at least partially, through the activation of NF-{kappa}B signaling in IECs. [PUBLICATION ABSTRACT]
ISSN:0363-6143
1522-1563