Specific binding of plasminogen to vitronectin. Evidence for a modulatory role of vitronectin on fibrin(ogen)-induced plasmin formation by tissue plasminogen activator.
Vitronectin immobilized onto polystyrene microtiter wells was demonstrated to specifically bind plasminogen in a concentration-dependent manner, yielding an estimated KD = 0.4 microM. Heparin only moderately interfered with the vitronectin-plasminogen interaction, whereas high concentrations of 6-amino-hexanoic acid inhibited binding. Utilizing a ligand-blotting procedure in which plasminogen was reacted with proteolytic fragments of vitronectin, transblotted onto nitrocellulose, the plasminogen-binding site of vitronectin was localized to the heparin-binding domain of the adhesive protein. Moreover, vitronectin was found to inhibit in a dose-dependent fashion the fibrin(ogen)-induced activation of plasminogen by tissue plasminogen activator. These results provide the first evidence for a novel vitronectin-mediated control of plasminogen activation potentially relevant for directional clot-lysis and plasmin-dependent proteolysis in extracellular matrices.
Clinical Research Unit for Blood Coagulation and Thrombosis, Max-Planck-Gesellschaft, Giessen, F.R.G.
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Preissner
D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005337:Fibrin / Q000037:antagonists & inhibitors / Q000502:physiology*; D005341:Fibrinolysin / Q000096:biosynthesis*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D010959:Tissue Plasminogen Activator / Q000502:physiology*; D019096:Vitronectin
D006023:Glycoproteins; D010446:Peptide Fragments; D019096:Vitronectin; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin