The intact urokinase receptor is required for efficient vitronectin binding: receptor cleavage prevents ligand interaction

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Abstract
The urokinase receptor (uPAR) is a receptor for both urokinase plasminogen activator (uPA) and the adhesion protein vitronectin. There are two forms of cell surface‐bound uPAR; intact uPAR and a cleaved form, uPAR(2+3), which is formed by uPA‐catalyzed cleavage of uPAR. In ligand‐blotting experiments we found that vitronectin binds uPAR but not uPAR(2+3). In real‐time biomolecular interaction analysis using recombinant, soluble uPAR (suPAR) both plasma and multimeric forms of vitronectin bound to intact, antibody‐immobilized suPAR. Monoclonal antibodies against domain 1 of uPAR blocked suPAR binding to vitronectin and vitronectin did not interact with suPAR(2+3). Both suPAR(2+3) and the isolated domain 1 failed to compete with the intact suPAR in binding to vitronectin. We therefore conclude that the intact receptor is required for efficient vitronectin binding.