Comparison of kinetic parameters of the activation of Glu-plasminogen by tissue plasminogen activator obtained from various sources.
Kinetic analyses were made for the activation of Glu-plasminogen (Glu-Plg) by tissue plasminogen activator (t-PA) obtained from various sources. We compared kinetic parameters for three t-PA preparations. t-PA(M) was obtained from cultured melanoma cell line, and t-PA(W) and t-PA(TD) were obtained from cells with recombinant DNA. t-PA(W) had two chains whereas t-PA(TD) had one chain. Although values of kinetic parameters were different in the three t-PA preparations, there were following general tendencies. The presence of catalytic amounts of fibrin resulted in a decrease in Km, whereas the presence of larger amounts of fibrin resulted in an increase in kcat with a slight decrease in Km. The presence of fibrinogen also enhanced the activation of Glu-Plg by t-PA with an increase in kcat and without change in Km. When the effects of fragment D or E were compared, the presence of increasing amounts of E resulted in an increase in kcat, but the presence of increasing amounts of D resulted in an increase in kcat and a decrease in Km. The results suggest that roles of D and E domains of fibrin may be different in the enhanced activation of plasminogen by t-PA.
D000818:Animals; D002384:Catalysis; D004274:DNA, Recombinant; D004591:Electrophoresis, Polyacrylamide Gel; D005337:Fibrin / Q000494:pharmacology; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology; D005340:Fibrinogen / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D051379:Mice; D010958:Plasminogen / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D004274:DNA, Recombinant; D005338:Fibrin Fibrinogen Degradation Products; C015214:fibrinogen D fragment; C018543:fibrinogen fragment E; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D013917:Thrombin; D010959:Tissue Plasminogen Activator