The activation of pro-urokinase by plasma kallikrein and its inactivation by thrombin.
The activation of pro-urokinase by plasma kallikrein and its inactivation by thrombin.
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发表时间：
1986-03
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通讯作者：
Akitada Ichinose;Kazuo Fujikawa;Tadakazu SuyamaS
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作者：
Akitada Ichinose;Kazuo Fujikawa;Tadakazu SuyamaS
血浆激肽释放酶被发现是尿激酶原（尿激酶的无活性酶原形式）的良好激活剂。血浆激肽释放酶在2小时内完全激活尿激酶原，酶/底物重量比为1/30。血浆激肽释放酶激活尿激酶原的速率与纤溶酶和胰蛋白酶催化的相当。因子 XIIa 激活尿激酶原的速率大约是血浆激肽释放酶激活尿激酶原的七分之一。酶原的激活是由于单个内部肽键的裂解，导致单链尿激酶原（Mr = 55,000）转化为双链尿激酶（Mr = 33,000和22,000），并且这两条链通过二硫键连接。这些结果表明血浆激肽释放酶对于激活XII因子依赖性纤维蛋白溶解内在途径中尿激酶原的重要作用。凝血酶还将尿激酶原转化为不能被纤溶酶、血浆激肽释放酶和因子 XIIa 激活的双链形式。凝血酶特异性裂解位于 Lys 158-Ile 159 激活位点之前 2 个残基的 Arg 156-Phe 157 键。
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.