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 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.
Høyer-Hansen
G
G
Finsen Laboratory, Rigshospitalet, Copenhagen O, Denmark.
Behrendt
N
N
Ploug
M
M
Danø
K
K
Preissner
K T
KT
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*
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