Redlitz A, Tan A K, Eaton D L, Plow E F
Department of Molecular Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA.
J Clin Invest. 1995 Nov;96(5):2534-8. doi: 10.1172/JCI118315.
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.
细胞表面和纤维蛋白上的羧基末端赖氨酸残基可结合纤溶酶原并控制其激活。由于血浆中含有碱性羧肽酶，可从蛋白质底物上除去羧基末端赖氨酸，因此我们研究了这些酶是否参与纤溶酶原结合位点的调节。血浆降低了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。组成型活性的纯化羧肽酶N和以酶原形式循环的血浆羧肽酶B均能够显著降低纤溶酶原与细胞的结合。剂量滴定实验证实，两种羧肽酶的血浆浓度均足以最大程度地影响纤溶酶原与细胞的结合。此外，血浆羧肽酶B而非羧肽酶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。这些发现表明，血浆羧肽酶可调节纤溶酶原与细胞的结合并控制纤维蛋白溶解速率。这些功能描绘了血浆羧肽酶在纤溶酶原系统调节中的新作用。
