X-linked inhibitor of apoptosis protein controls alpha(5)-integrin-mediated cell adhesion and migration

Abstract

Kim J, Ahn S, Ko YG, Boo YC, Chi SG, Ni CW, Go YM, Jo H, Park H. X-linked inhibitor of apoptosis protein controls alpha(5)-integrin-mediated cell adhesion and migration. Am J Physiol Heart Circ Physiol 299: H300-H309, 2010. First published May 14, 2010; doi:10.1152/ajpheart.00180.2010.-The association of integrins with caveolin-1 regulates cell adhesion. However, the vascular ramifications of this association remain to be clearly determined. We recently reported that the X chromosome-linked inhibitor of apoptosis protein (XIAP)-caveolin-1 interaction is critical to endothelial cell survival. Thus, we hypothesized that XIAP performs a crucial function in integrin/caveolin-1-mediated endothelial cell survival. In this study, we demonstrated that XIAP is recruited into the alpha(5)-integrin complex via caveolin-1 binding and mediates cell adhesion. We also determined that XIAP is critical to shear stress-stimulated ERK activation in an alpha(5)-integrin-dependent manner but is not important to VEGF-induced ERK activation. This differential activation of ERK is partly attributable to unique localizations of the receptors. Furthermore, we confirmed that XIAP is an essential molecule in the efficient recruitment of focal adhesion kinase (FAK) into the alpha(5)-integrin-associated complex. This alpha(5)-integrin-caveol