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

TY - JOUR

T1 - The intact urokinase receptor is required for efficient vitronectin binding

T2 - receptor cleavage prevents ligand interaction

AU - Høyer-Hansen, G

AU - Behrendt, N

AU - Ploug, M

AU - Danø, K

AU - Preissner, Klaus T

PY - 1997/12/22

Y1 - 1997/12/22

N2 - 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.

AB - 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.

KW - Antibodies, Monoclonal

KW - Binding, Competitive

KW - Biosensing Techniques

KW - Humans

KW - Ligands

KW - Neuraminidase

KW - Plasminogen Activator Inhibitor 1

KW - Receptors, Cell Surface

KW - Receptors, Urokinase Plasminogen Activator

KW - Solubility

KW - Urokinase-Type Plasminogen Activator

KW - Vitronectin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Journal article

C2 - 9450554

SN - 0014-5793

VL - 420

SP - 79

EP - 85

JO - F E B S Letters

JF - F E B S Letters

IS - 1

ER -