X-linked inhibitor of apoptosis protein controls α 5- integrin-mediated cell adhesion and migration

Jongmin Kim, Sunyoung Ahn, Young Gyu Ko, Yong Chool Boo, Sung Gil Chi, Chih Wen Ni, Young Mi Go, Hanjoong Jo, Heonyong Park

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 α 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 α 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 α 5-integrin-associated complex. This α 5-integrin-caveolin-1-XIAP-FAK multi-complex regulates endothelial cell migration via a mechanism that involves shear-dependent ERK activation. Together, our results indicate that XIAP stabilizes the α 5-integrin-associated focal adhesion complex, thereby further regulating endothelial cell adhesion and migration. The findings of this study provide us with greater insight into the molecular mechanisms underlying the control of vascular function by integrins.

Original languageEnglish
Pages (from-to)H300-H309
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number2
DOIs
Publication statusPublished - 2010 Aug

Keywords

  • Endothelial cells
  • Extracellular signal-regulated kinase
  • Focal adhesion kinase
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'X-linked inhibitor of apoptosis protein controls α <sub>5</sub>- integrin-mediated cell adhesion and migration'. Together they form a unique fingerprint.

  • Cite this