ACCESSIBILITY OF RECEPTOR-BOUND UROKINASE TO TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR
ACCESSIBILITY OF RECEPTOR-BOUND UROKINASE TO TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR
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DOI：
10.1073/pnas.86.13.4828
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发表时间：
1989-07-01
影响因子：
11.1
通讯作者：
BLASI, F
中科院分区：
文献类型：
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作者：
CUBELLIS, MV;ANDREASEN, P;BLASI, F
尿激酶纤溶酶原激活剂（uPA）与表面受体和特异性抑制剂相互作用，如1型纤溶酶原激活剂抑制剂（PAI-1）。这些相互作用由分子的两个功能独立的结构域介导：催化结构域（在羧基端）和生长因子结构域（在氨基端）。我们现在研究了PAI-1是否可以结合和抑制受体结合的uPA。125i标记的ATF （uPA的氨基末端片段）与人U937单核细胞样细胞的结合可以被uPA-PAI-1复合物竞争，但不能被PAI-1单独竞争。预先形成的125i标记的uPA- pai -1复合物可以以与uPA相同的结合特异性与uPA受体结合。在U937细胞中，PAI-1也结合并抑制受体结合的uPA的活性，如酪蛋白溶斑试验所示。这些细胞的纤溶酶原激活剂的活性依赖于外源性uPA，与受体结合的氟磷酸二异丙基处理的uPA竞争，并被PAI-1的加入抑制。综上所述，在U937细胞中，与受体的结合并不能保护uPA免受PAI-1的作用。在贴壁细胞中，PAI-1和uPA的不同定位可能导致uPA免受PAI-1的保护。
Urokinase plasminogen activator (uPA) interacts with a surface receptor and with specific inhibitors, such as plasminogen activator inhibitor type 1 (PAI-1). These interactions are mediated by two functionally independent domains of the molecule: the catalytic domain (at the carboxyl terminus) and the growth factor domain (at the amino terminus). We have now investigated whether PAI-1 can bind and inhibit receptor-bound uPA. Binding of 125I-labeled ATF (amino-terminal fragment of uPA) to human U937 monocyte-like cells can be competed for by uPA-PAI-1 complexes, but not by PAI-1 alone. Preformed 125I-labeled uPA-PAI-1 complexes can bind to uPA receptor with the same binding specificity as uPA. PAI-1 also binds to, and inhibits the activity of, receptor-bound uPA in U937 cells, as shown in U937 cells by a caseinolytic plaque assay. Plasminogen activator activity of these cells is dependent on exogenous uPA, is competed for by receptor-binding diisopropyl fluorophosphate-treated uPA, and is inhibited by the addition of PAI-1. In conclusion, in U937 cells the binding to the receptor does not shield uPA from the action of PAI-1. The possibility that in adherent cells a different localization of PAI-1 and uPA leads to protection of uPA from PAI-1 is to be considered.