Regulation of urokinase receptor function and pericellular proteolysis by the integrin alpha(5)beta(1).

Bass, Rosemary and Ellis, Vincent (2009) Regulation of urokinase receptor function and pericellular proteolysis by the integrin alpha(5)beta(1). 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 alpha(5)beta(1), 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 alpha(5)beta(1) cellular localisation. Here we have investigated whether overexpression of alpha(5)beta(1) directly affects uPAR-dependent pericellular proteolysis. CHO cells overexpressing alpha(5)beta(1) were found to activate plasminogen at a rate up to 18-fold faster than B2CHO cells which are alpha(5)-deficient. This effect was dependent on the activation state of alpha(5)beta(1), as it was maximal in the presence of Mn(2+). To determine the role of uPAR-alpha(5)beta(1) 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 alpha(5)beta(1), possibly implicating the involvement of non-alpha(5)-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 alpha(5)beta(1) 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 uPAR-dependent 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
Subjects:	A100 Pre-clinical Medicine C700 Molecular Biology, Biophysics and Biochemistry C900 Others in Biological Sciences
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Ay Okpokam
Date Deposited:	11 Jan 2012 13:20
Last Modified:	12 Oct 2019 18:25
URI:	http://nrl.northumbria.ac.uk/id/eprint/4475

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