| 16354757 |
Zhang HM, Keledjian KM, Rao JN, Zou T, Liu L, Marasa BS, Wang SR, Ru L, Strauch ED, Wang JY: Induced focal adhesion kinase expression suppresses apoptosis by activating NF-kappaB signaling in intestinal epithelial cells. Am J Physiol Cell Physiol. 2006 May;290(5):C1310-20. Epub 2005 Dec 14.
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-kappaB 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-kappaB 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-kappaB by the recombinant adenoviral vector containing the IkappaBalpha 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-kappaB activity and increased the sensitivity to TNF-alpha/CHX-induced apoptosis. Furthermore, induced expression of endogenous FAK by depletion of cellular polyamines increased NF-kappaB 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-kappaB signaling in IECs. |
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