The activation of pro-urokinase by plasma kallikrein and its inactivation by thrombin.
Plasma kallikrein was found to be a good activator of pro-urokinase, the inactive zymogen form of urokinase. The complete activation of pro-urokinase by plasma kallikrein was obtained in 2 h with an enzyme/substrate weight ratio of 1/30. The rate of activation of pro-urokinase by plasma kallikrein was comparable to that catalyzed by plasmin and trypsin. The rate of activation of pro-urokinase by factor XIIa was approximately one-seventh of that by plasma kallikrein. The activation of the zymogen was due to the cleavage of a single internal peptide bond, resulting in the conversion of a single chain pro-urokinase (Mr = 55,000) into two-chain urokinase (Mr = 33,000 and 22,000), and these two chains were linked by a disulfide bond(s). These results indicate an important role of plasma kallikrein for the activation of pro-urokinase in the factor XII-dependent intrinsic pathway of fibrinolysis. Thrombin also converted pro-urokinase to a two-chain form that was not activatable by plasmin, plasma kallikrein, and factor XIIa. Thrombin specifically cleaved the Arg 156-Phe 157 bond which is located 2 residues prior to the activation site of Lys 158-Ile 159.
Ichinose
A
A
Fujikawa
K
K
Suyama
T
T
D000595:Amino Acid Sequence; D004789:Enzyme Activation; D005174:Factor XII / Q000494:pharmacology; D015956:Factor XIIa; D005342:Fibrinolysis; D007610:Kallikreins / Q000494:pharmacology*; D008970:Molecular Weight; D010446:Peptide Fragments / Q000494:pharmacology; D010960:Plasminogen Activators / Q000032:analysis* / Q000037:antagonists & inhibitors; D015849:Plasminogen Inactivators; D013917:Thrombin / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis* / Q000037:antagonists & inhibitors
D010446:Peptide Fragments; D015849:Plasminogen Inactivators; D005174:Factor XII; D007610:Kallikreins; D010960:Plasminogen Activators; D015956:Factor XIIa; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator