| First Author | Monaghan-Benson E | Year | 2008 |
| Journal | J Cell Sci | Volume | 121 |
| Issue | Pt 22 | Pages | 3693-703 |
| PubMed ID | 18957516 | Mgi Jnum | J:145772 |
| Mgi Id | MGI:3836067 | Doi | 10.1242/jcs.028423 |
| Citation | Monaghan-Benson E, et al. (2008) A dual role for caveolin-1 in the regulation of fibronectin matrix assembly by uPAR. J Cell Sci 121(Pt 22):3693-703 |
| abstractText | The relationship between the plasminogen activator system and integrin function is well documented but incompletely understood. The mechanism of uPAR-mediated signaling across the membrane and the molecular basis of uPAR-dependent activation of integrins remain important issues. The present study was undertaken to identify the molecular intermediates involved in the uPAR signaling pathway controlling alpha5beta1-integrin activation and fibronectin polymerization. Disruption of lipid rafts with MbetaCD or depletion of caveolin-1 by siRNA led to the inhibition of uPAR-dependent integrin activation and stimulation of fibronectin polymerization in human dermal fibroblasts. The data indicate a dual role for caveolin-1 in the uPAR signaling pathway, leading to integrin activation. Caveolin-1 functions initially as a membrane adaptor or scaffold to mediate uPAR-dependent activation of Src and EGFR. Subsequently, in its phosphorylated form, caveolin-1 acts as an accessory molecule to direct trafficking of activated EGFR to focal adhesions. These studies provide a novel paradigm for the regulation of crosstalk among integrins, growth-factor receptors and uPAR. |
