Inhibition of urokinase activity and prevention of urokinase receptor binding by monoclonal antibodies.
Two murine monoclonal antibodies produced against human urokinase-type plasminogen activator were characterized with respect to their antigen-binding specificity and their effects on urokinase activity and urokinase receptor binding. One of the antibodies binds to the protease domain of urokinase (Kass = 2.1 X 10(7) M-1). Antibody binding inhibits catalysis of plasminogen activation. It does not, however, affect amidolytic activity of urokinase towards the chromogenic substrate D-Val-Leu-Arg-p-nitroanilide. The antibody thus appears to interfere with plasminogen binding without directly affecting catalytically active amino acid residues of the enzyme. The other antibody binds to the aminoterminal fragment of urokinase (Kass = 1.0 X 10(7) M-1) and prevents binding of the enzyme to high affinity receptors on human granulocytes. Binding of this antibody neither influences plasminogen activation nor the amidolytic activity of urokinase. Both antibodies are potentially useful for the further analysis and manipulation of urokinase function.
Zacharias
U
U
Central Institute of Molecular Biology, Academy of Sciences of the GDR, Berlin-Buch.
Handschack
W
W
Schneider
F
F
Löster
K
K
Kleitke
C
C
Noll
F
F
Will
H
H
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D015153:Blotting, Western; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000276:immunology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator