Anglés-Cano E
Institut National de la Santé et de la Recherche Médicale (INSERM) U. 143, Hôpital de Bicêtre, France.
Chem Phys Lipids. 1994 Jan;67-68:353-62. doi: 10.1016/0009-3084(94)90157-0.
Plasminogen activation at the surface of fibrin or of cell membranes is a sophisticated specialized system for localized extracellular proteolysis implicated in a large variety of biological functions (fibrinolysis, cell migration and extracellular matrix degradation). Assembly of plasminogen and/or activators at specific binding sites induces conformational changes that make accessible the scissile peptide bond of plasminogen and exposes the active centre of the tissue-type plasminogen activator. The mechanism of activation by pro-urokinase, a second type of activator that binds to cell membrane but not to fibrin, is far from being understood. It may be able, however, in contrast to urokinase, to specifically activate plasminogen bound to partially degraded fibrin. An extremely low Km and high catalytic rate are characteristic of the process of activation at surfaces. In contrast, activation in liquid phase by tissue-type plasminogen activator proceeds at an extremely low catalytic rate. The initiation and amplification of plasminogen activation depend on specific interactions between the modular constitutive units of these proteins and binding sites present on cell or fibrin surfaces. Thus, the most important mechanism for the acceleration of fibrinolysis and pericellular proteolysis is the unveiling of carboxy-terminal lysine residues on these surfaces, to which plasminogen may bind. Since plasminogen bound to carboxy-terminal lysines of progressively degraded fibrin or membranes is readily transformed into plasmin by fibrin-bound t-PA, this mechanism represents the most important pathway for the acceleration and amplification of fibrinolysis. Alpha-2-antiplasmin, by inhibiting plasmin release from surfaces, regulates the extent and rate of this process but has no effect on fibrin-bound or membrane-bound plasmin. Lipoprotein(a), a particle possessing a plasminogen-like apolipoprotein, apo(a), may interfere with this mechanism by inhibiting the specific binding of plasminogen to lysine residues in membrane or fibrin surfaces.
纤维蛋白或细胞膜表面的纤溶酶原激活是一种复杂的局部细胞外蛋白水解专门系统，涉及多种生物学功能（纤维蛋白溶解、细胞迁移和细胞外基质降解）。纤溶酶原和/或激活剂在特定结合位点的组装会引起构象变化，使纤溶酶原的可裂解肽键易于接近，并暴露出组织型纤溶酶原激活剂的活性中心。前尿激酶是另一种与细胞膜而非纤维蛋白结合的激活剂，其激活机制尚不清楚。然而，与尿激酶不同，它可能能够特异性激活与部分降解的纤维蛋白结合的纤溶酶原。表面激活过程的特点是极低的米氏常数和高催化速率。相比之下，组织型纤溶酶原激活剂在液相中的激活以极低的催化速率进行。纤溶酶原激活的起始和放大取决于这些蛋白质的模块化组成单元与细胞或纤维蛋白表面存在的结合位点之间的特异性相互作用。因此，加速纤维蛋白溶解和细胞周围蛋白水解的最重要机制是这些表面上羧基末端赖氨酸残基的暴露，纤溶酶原可与之结合。由于与逐渐降解的纤维蛋白或膜的羧基末端赖氨酸结合的纤溶酶原很容易被纤维蛋白结合的组织型纤溶酶原激活剂转化为纤溶酶，因此该机制代表了加速和放大纤维蛋白溶解的最重要途径。α2抗纤溶酶通过抑制纤溶酶从表面释放来调节这一过程的程度和速率，但对纤维蛋白结合或膜结合的纤溶酶没有影响。脂蛋白(a)是一种含有类纤溶酶原载脂蛋白apo(a)的颗粒，它可能通过抑制纤溶酶原与膜或纤维蛋白表面赖氨酸残基的特异性结合来干扰这一机制。
