title: The intact urokinase receptor is required for efficient vitronectin binding: receptor cleavage prevents ligand interaction.
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.
authors.affiliation: Finsen Laboratory, Rigshospitalet, Copenhagen O, Denmark.
authors.forename: G
authors.initials: G
authors.lastname: Høyer-Hansen
authors.forename: N
authors.initials: N
authors.lastname: Behrendt
authors.forename: M
authors.initials: M
authors.lastname: Ploug
authors.forename: K
authors.initials: K
authors.lastname: Danø
authors.forename: K T
authors.initials: KT
authors.lastname: Preissner
mesh_terms: D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D015374:Biosensing Techniques; D006801:Humans; D008024:Ligands; D009439:Neuraminidase; D017395:Plasminogen Activator Inhibitor 1 / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D012995:Solubility; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D008024:Ligands; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin; D009439:Neuraminidase; D014568:Urokinase-Type Plasminogen Activator