An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation.
An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation.
复制标题
DOI：
--
复制
发表时间：
1994-08
期刊：
影响因子：
--
通讯作者：
G. Cesarman;C. A. Guevara;K. Hajjar
中科院分区：
文献类型：
--
作者：
G. Cesarman;C. A. Guevara;K. Hajjar
在前面的论文（Hajjar，K.一、Jacovina，A. T.，和Chacko，J.（1994）J.Biol.Chem.269，21191-21197），我们鉴定了M（r）= 40，000的组织纤溶酶原激活物（t-PA）和纤溶酶原（PLG）的内皮细胞受体作为钙和磷脂结合蛋白，膜联蛋白II（Ann-II）。在这里，我们研究了在纯化系统中Ann-II对t-PA依赖性纤溶酶原激活的影响。纯化的天然Ann-II以高亲和力结合t-PA、纤溶酶原和纤溶酶（Kd分别为25 nM、161 nM和75 nM）。在固定的纤溶酶原浓度下，用纯化的天然Ann-II预孵育与Glu-PLG活化速率增加约21倍和Lys-PLG活化增加约14倍相关。三个不相关的蛋白质对纤溶酶的形成没有影响，而纤维蛋白原使Glu-PLG活化的速率增加了约4倍。ε-氨基己酸或用羧肽酶B预处理Ann-II可抑制Annexin-II介导的t-PA依赖性纤溶酶原激活增强作用90-95%，表明存在羧基末端赖氨酸依赖性相互作用。动力学分析表明，Ann-II赋予约60倍的催化效率增加后，t-PA依赖性激活的Glu-PLG或Lys-PLG。因此，Ann-II介导的纤溶酶原和t-PA的组装可以促进和定位在血管壁表面上的组成型纤溶酶的产生。
In the preceding paper (Hajjar, K. A., Jacovina, A. T., and Chacko, J. (1994) J. Biol. Chem. 269, 21191-21197), we identified a M(r) = 40,000 endothelial cell receptor for tissue plasminogen activator (t-PA) and plasminogen (PLG) as the calcium- and phospholipid-binding protein, annexin II (Ann-II). Here, we examined the effect of Ann-II on t-PA-dependent plasminogen activation in a purified system. Purified native Ann-II bound t-PA, plasminogen, and plasmin with high affinity (Kd = 25 nM, 161 nM, and 75 nM, respectively). At fixed plasminogen concentrations, preincubation with purified native Ann-II was associated with an approximately 21-fold increase in the rate of Glu-PLG activation and an approximately 14-fold increase in activation of Lys-PLG. Three irrelevant proteins had no effect on plasmin formation, while fibrinogen increased the rate of Glu-PLG activation by approximately 4-fold. Annexin-II-mediated enhancement of t-PA-dependent plasminogen activation was 90-95% inhibited by epsilon-aminocaproic acid or by pretreatment of Ann-II with carboxypeptidase B, indicating a carboxyl-terminal lysine-dependent interaction. Kinetic analyses revealed that Ann-II conferred an approximately 60-fold increase in catalytic efficiency upon t-PA-dependent activation of either Glu-PLG or Lys-PLG. Thus, Ann-II-mediated assembly of plasminogen and t-PA may promote and localize constitutive plasmin generation on the surface of the blood vessel wall.