THE INTACT UROKINASE RECEPTOR IS REQUIRED FOR EFFICIENT VITRONECTIN BINDING - RECEPTOR CLEAVAGE PREVENTS LIGAND INTERACTION

The urokinase receptor (uPAR) is a receptor for both urokinase plasmin ogen activator (uPA) and the adhesion protein vitronectin. There are t wo forms of cell surface-bound uPAR; intact uPAR and a cleaved form, u PAR(2+3), which is formed by uPA-catalyzed cleavage of uPAR. In ligand -blotting experiments we found that vitronectin binds uPAR but not uPA R(2+3). In real-time biomolecular interaction analysis using recombina nt, soluble uPAR (suPAR) both plasma and multimeric forms of vitronect in bound to intact, antibody-immobilized suPAR, Monoclonal antibodies against domain 1 of uPAR blocked suPAR binding to vitronectin and vitr onectin did not interact with suPAR(2+3). Both suPAR(2+3) and the isol ated domain 1 failed to compete with the intact suPAR in binding to vi tronectin. We therefore conclude that the intact receptor is required for efficient vitronectin binding. (C) 1997 Federation of European Bio chemical Societies.