X-linked inhibitor of apoptosis protein controls alpha5-integrin-mediated cell adhesion and migration.
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-caveolin-1-XIAP-FAK multicomplex regulates endothelial cell migration via a mechanism that involves shear-dependent ERK activation. Together, our results indicate that XIAP stabilizes the alpha(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.
Kim
Jongmin
J
Dept. of Molecular Biology and Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook Univiersity, 126, Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do 448-701, Korea.
Ahn
Sunyoung
S
Ko
Young-Gyu
YG
Boo
Yong Chool
YC
Chi
Sung-Gil
SG
Ni
Chih-Wen
CW
Go
Young-Mi
YM
Jo
Hanjoong
H
Park
Heonyong
H
D000818:Animals; D002417:Cattle; D051242:Caveolin 1 / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism*; D046912:Multiprotein Complexes; D009154:Mutation; D009842:Oligopeptides / Q000378:metabolism; D034622:RNA Interference; D013314:Stress, Mechanical; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism*
D051242:Caveolin 1; D039482:Integrin alpha5; D046912:Multiprotein Complexes; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; D051636:X-Linked Inhibitor of Apoptosis Protein; C047981:arginyl-glycyl-aspartic acid; D040301:Vascular Endothelial Growth Factor Receptor-2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
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