Wun T C
Department of Biological Sciences, Monsanto Co., Chesterfield, Missouri.
Crit Rev Biotechnol. 1988;8(2):131-48. doi: 10.3109/07388558809150542.
The mammalian serine protease zymogen, plasminogen, can be converted into the active enzyme plasmin by vertebrate plasminogen activators urokinase (uPA), tissue plasminogen activator (tPA), factor XII-dependent components, or by bacterial streptokinase. The biochemical properties of the major components of the system, plasminogen/plasmin, plasminogen activators, and inhibitors of the plasminogen activators, are reviewed. The plasmin system has been implicated in a variety of physiological and pathological processes such as fibrinolysis, tissue remodeling, cell migration, inflammation, and tumor invasion and metastasis. A defective plasminogen activator/inhibitor system also has been linked to some thromboembolic complications. Recent studies of the mechanism of fibrinolysis in human plasma suggest that tPA may be the primary initiator and that overall fibrinolytic activity is strongly regulated at the tPA level. A simple model for the initiation and regulation of plasma fibrinolysis based on these studies has been formulated. The plasminogen activators have been used for thrombolytic therapy. Three new thrombolytic agents--tPA, pro-uPA, and acylated streptokinase-plasminogen complex--have been found to possess better properties over their predecessors, urokinase and streptokinase. Further improvements of these molecules using genetic and protein engineering tactics are being pursued.
哺乳动物丝氨酸蛋白酶原——纤溶酶原，可被脊椎动物纤溶酶原激活物尿激酶（uPA）、组织纤溶酶原激活物（tPA）、因子Ⅻ依赖性成分或细菌链激酶转化为活性酶纤溶酶。本文综述了该系统主要成分——纤溶酶原/纤溶酶、纤溶酶原激活物以及纤溶酶原激活物抑制剂的生化特性。纤溶酶系统参与了多种生理和病理过程，如纤维蛋白溶解、组织重塑、细胞迁移、炎症以及肿瘤侵袭和转移。纤溶酶原激活物/抑制剂系统缺陷也与一些血栓栓塞并发症有关。近期关于人血浆纤维蛋白溶解机制的研究表明，tPA可能是主要启动因子，且整体纤维蛋白溶解活性在tPA水平受到强烈调控。基于这些研究，已构建了一个血浆纤维蛋白溶解启动和调控的简单模型。纤溶酶原激活物已用于溶栓治疗。已发现三种新型溶栓剂——tPA、单链尿激酶型纤溶酶原激活剂（pro - uPA）和酰化链激酶 - 纤溶酶原复合物——相较于其前身尿激酶和链激酶具有更好的特性。目前正在采用基因和蛋白质工程策略对这些分子进行进一步改进。
