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

Wei Ying, Xiuwei Yang, Liu Qiumei, John A. Wilkins, Harold A. Chapman

Research output: Contribution to journalArticlepeer-review

373 Scopus citations

Abstract

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 β1 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 β1 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 β1 integrin/caveolin complexes. Depletion of caveolin in uPAR- expressing 293 cells also disrupts uPAR/integrin complexes and uPAR-dependent adhesion. Further, β1 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 β1 integrins and markedly impairs their migration on fibronectin. We conclude that ligand- induced signaling necessary for normal β1 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.

Original languageEnglish
Pages (from-to)1285-1294
Number of pages10
JournalJournal of Cell Biology
Volume144
Issue number6
DOIs
StatePublished - Mar 22 1999

Keywords

  • Adhesion
  • Caveolin
  • Cell signaling
  • Integrins
  • Urokinase receptor

ASJC Scopus subject areas

  • Cell Biology

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