Thrombin-mediated mitogenesis: the role of secreted protease nexin.
Thrombin-mediated mitogenesis: the role of secreted protease nexin.
复制标题
凝血酶介导的有丝分裂发生：分泌型蛋白酶连接蛋白的作用。
DOI：
10.1002/jcp.1041120220
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发表时间：
1982
影响因子：
5.6
通讯作者：
Cunningham,DD
中科院分区：
文献类型：
--
作者：
Baker,JB;Low,DA;Eaton,DL;Cunningham,DD
蛋白酶连接蛋白（PN）是一种细胞分泌的蛋白质，与凝血酶（Th）和某些其他丝氨酸蛋白酶连接。PN介导细胞对这些蛋白酶的结合、内化和降解（Baker等人，1980; Low等人，1981年）。在这里，我们表明，结合的Th-PN复合物的人包皮成纤维细胞（HF细胞）占90%的特定细胞Th结合在某些促有丝分裂剂量的蛋白酶。然而，细胞相关的Th-PN复合物可能无促有丝分裂活性，因为肝素（170单位/ml）抑制细胞结合125-Th-PN约95%（从1.3× 105减少到6× 103 125 I-Th-PN复合物/细胞），但不影响Th介导的促有丝分裂刺激。在小鼠胚胎细胞的实验中，肝素也显着降低125 I-Th-PN的细胞结合，而不改变对Th的促有丝分裂反应。细胞相关的Th-PN复合物缺乏促有丝分裂活性，表明PN可能抑制Th的促有丝分裂必需的蛋白水解活性。这一可能性得到以下调查结果的支持。首先，含有足够PN以复合大部分添加的Th的无血清条件培养基的量抑制Th的凝血活性。第二，肝素增加了125 I-Th-PN复合物的形成，也增加了条件培养基的这种抑制作用。我们得出结论，PN作为凝血酶促有丝分裂活性的负调制器。
Protease nexin (PN) is a cell-secreted protein that links to thrombin (Th) and certain other serine proteases. PN mediates the binding, internalization, and degradation of these proteases by cells (Baker et al., 1980; Low et al., 1981). Here we show that binding of Th-PN complexes to human foreskin fibroblasts (HF cells) accounted for 90% of the specific cellular Th binding at certain mitogenic doses of the protease. However, cell-associated Th-PN complexes were likely to be inactive mitogenically because heparin (170 units/ml) inhibited cellular binding of 125-Th-PN by about 95%(a reduction from 1.3× 10 5 to 6× 10 3 125 I-Th-PN complexes per cell) but did not influence Th-mediated mitogenic stimulation. In experiments with mouse embryo cells, heparin also markedly decreased cellular binding of 125 I-Th-PN without changing the mitogenic response to Th. The lack of mitogenic activity of cell-associated Th-PN complexes suggested that PN might inhibit the mitogenically essential proteolytic activity of Th. This possibility is supported by the following findings. First, amounts of serum-free conditioned culture medium that contained enough PN to complex a large fraction of added Th inhibited the clotting activity of Th. Second, heparin increased the formation of 125 I-Th-PN complexes and also increased this inhibitory effect of conditioned medium. We conclude that PN acts as a negative modulator of thrombin mitogenic activity.