A role for caveolin and the urokinase receptor in integrin-mediated adhesion and signaling

被引:352
作者
Wei, Y
Yang, XW
Liu, QM
Wilkins, JA
Chapman, HA
机构
[1] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Univ Manitoba, Dept Internal Med, Winnipeg, MB R3A 1M4, Canada
关键词
urokinase receptor; caveolin; integrins; adhesion; cell signaling;
D O I
10.1083/jcb.144.6.1285
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The assembly of signaling molecules surrounding the integrin family of adhesion receptors remains poorly understood. Recently, the membrane protein caveolin was found in complexes with beta 1 integrins. Caveolin binds cholesterol and several signaling molecules potentially linked to integrin function, e.g., Src family kinases, although caveolin has not been directly implicated in integrin-dependent adhesion. Here we report that depletion of caveolin by antisense methodology in kidney 293 cells disrupts the association of Src kinases with beta 1 integrins resulting in loss of focal adhesion sites, ligand-induced focal adhesion kinase (FAK) phosphorylation, and adhesion. The nonintegrin urokinase receptor (uPAR) associates with and stabilizes beta 1 integrin/caveolin complexes. Depletion of caveolin in uPAR-expressing 293 cells also disrupts uPAR/integrin complexes and uPAR-dependent adhesion. Further, beta 1 integrin/caveolin complexes could be disassociated by uPAR-binding peptides in both uPAR-transfected 293 cells and human vascular smooth muscle cells. Disruption of complexes by peptides in intact smooth muscle cells blocks the association of Src family kinases with beta 1 integrins and markedly impairs their migration on fibronectin. We conclude that ligand-induced signaling necessary for normal beta 1 integrin function requires caveolin and is regulated by uPAR. Caveolin and uPAR may operate within adhesion sites to organize kinase-rich lipid domains in proximity to integrins, promoting efficient signal transduction.
引用
收藏
页码:1285 / 1294
页数:10
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