Regulation of urokinase receptor function and pericellular proteolysis by the integrin α5β1

Bass, R and Ellis, V (2009) Regulation of urokinase receptor function and pericellular proteolysis by the integrin α5β1. Thrombosis and Haemostasis, 101 (5). pp. 954-962. ISSN 0340-6245

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    Abstract

    Interactions between the uPA receptor (uPAR) and various integrins, including a5ß1, are known to modulate integrin-dependent cell adhesion, and we have shown that the integrin-associated tetraspanin protein CD82 down-regulates uPAR-dependent plasminogen activation by affecting a5ß1 cellular localisation. Here we have investigated whether overexpression of a5ß1 directly affects uPAR-dependent pericellular proteolysis. CHO cells overexpressing a5ß1 were found to activate plasminogen at a rate up to 18-fold faster than B2CHO cells which are a5-deficient. This effect was dependent on the activation state of a5ß1, as it was maximal in the presence of Mn2+. To determine the role of uPAR-a5ß1 interactions in this effect, we determined the adhesion of these cells to immobilised soluble uPAR (suPAR). Neither cell-type was found to adhere to suPAR, but both cell types were found to adhere to an anti-uPAR monoclonal antibody in a uPAR- and integrin-dependent manner. This adhesion was 10-fold greater in the absence of a5ß1, possibly implicating the involvement of non-a5-integrins. Soluble forms of the various components were used to investigate the molecular basis of these effects, but no direct interactions could be demonstrated between a5ß1 and either uPAR, uPA or uPA-uPAR complex. This suggests that assembly of these components on the plasma membrane is required to influence uPAR function, increasing uPAR-dependent pericellular proteolysis and decreasing uPARdependent cell adhesion. These interactions may be modified by other integrins, suggesting a complex interplay between uPAR and integrins on the cell surface with the potential to regulate invasive cell migration.

    Item Type: Article
    Faculty \ School: Faculty of Science > School of Biological Sciences
    Related URLs:
    Depositing User: Deborah Clemitshaw
    Date Deposited: 23 May 2011 14:26
    Last Modified: 25 Jul 2018 04:40
    URI: https://ueaeprints.uea.ac.uk/id/eprint/31262
    DOI: 10.1160/TH08-08-0558

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