Activation of fibrin-bound plasminogen by pro-urokinase and its complementariness with that by tissue plasminogen activator.
Single chain urokinase (SC-UK) is a precursor of 55 kd two-chain UK (TC-UK). Treatment with catalytic proportions of plasmin or kallikrein converts SC-UK to TC-UK as a consequence of cleavage of its Lys158-Ile159 peptide bond. This plasmin-mediated activation of SC-UK induces a positive feedback secondary reaction and complicates measurement of its activity against its natural substrate, Glu-plasminogen. The fibrin-selective effect of pro-UK-induced clot lysis is not related to fibrin binding. Rather, a conformational change in Glu-plasminogen, conferred when it binds to certain carboxy-terminal lysine residues on fibrin, has been implicated in this mechanism. This is complementary to t-PA. Fibrin-bound t-PA was found to exclusively activate plasminogen bound to certain internal lysine residues. Their complementariness is believed to explain their synergism in fibrinolysis.
Gurewich
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St. Elizabeth's Hospital, Department of Vascular Medicine, Boston, Mass.
D001777:Blood Coagulation / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004357:Drug Synergism; D005337:Fibrin / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D010960:Plasminogen Activators / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D005337:Fibrin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator