PLASMA CARBOXYPEPTIDASES AS REGULATORS OF THE PLASMINOGEN SYSTEM
PLASMA CARBOXYPEPTIDASES AS REGULATORS OF THE PLASMINOGEN SYSTEM
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DOI：
10.1172/jci118315
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发表时间：
1995-11-01
影响因子：
15.9
通讯作者：
PLOW, EF
中科院分区：
文献类型：
--
作者：
REDLITZ, A;TAN, AK;PLOW, EF
细胞表面和纤维蛋白表面的羧基末端赖氨酸残基结合纤溶酶原并控制其活化。由于血浆中含有碱性羧肽酶，可从蛋白质底物中去除羧基末端赖氨酸，我们研究了这些酶是否参与纤溶酶原结合位点的调节。血浆减少纤溶酶原与细胞的结合，这种作用可归因于血浆羧肽酶的活性。纯化的组成型活性羧肽酶N和作为酶原循环的血浆羧肽酶B均能显著降低纤溶酶原与细胞的结合。剂量滴定实验证实，任一羧肽酶的血浆浓度足以最大限度地影响纤溶酶原与细胞的结合。此外，血浆羧肽酶B，而不是羧肽酶N，降低了组织型纤溶酶原激活剂诱导的全血凝块溶解速率。这些发现证实血浆羧肽酶可以调节纤溶酶原与细胞的结合并控制纤溶速率。这些功能描绘了一个新的作用，血浆羧肽酶在纤溶酶原系统的调节。
Carboxy-terminal lysine residues on the surface of cells and fibrin bind plasminogen and control its activation. Since plasma contains basic carboxypeptidases, which remove carboxy-terminal lysines from protein substrates, we investigated if these enzymes are involved in the regulation of plasminogen binding sites, Plasma reduced plasminogen binding to cells, and this effect could be ascribed to the activity of the plasma carboxypeptidases. Purified carboxypeptidase N, which is constitutively active, and plasma carboxypeptidase B, which circulates as a zymogen, were both capable of significantly reducing plasminogen binding to cells. Dose titration experiments verified that plasma concentrations of either carboxypeptidase were sufficient to maximally affect plasminogen binding to cells, Furthermore, plasma carboxypeptidase B, but not carboxypeptidase N, reduced the rate of whole blood clot lysis induced by tissue-type plasminogen activator. These findings establish that plasma carboxypeptidases can modulate plasminogen binding to cells and control the rate of fibrinolysis. These functions delineate a novel role for the plasma carboxypeptidases in the regulation of the plasminogen system.