Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor
Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor
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DOI：
10.1074/jbc.272.10.6370
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发表时间：
1997-03-07
影响因子：
4.8
通讯作者：
Kitamura, N
中科院分区：
文献类型：
--
作者：
Shimomura, T;Denda, K;Kitamura, N
肝细胞生长因子（HGF）激活剂是一种丝氨酸蛋白酶，由肝脏产生和分泌，并作为无活性的酶原在血液中循环。为了响应组织损伤，HGF 激活酶原通过有限的蛋白水解转化为活性形式。激活的HGF激活剂在损伤组织中将HGF的无活性单链前体转化为具有生物活性的异二聚体，激活的HGF可能参与损伤组织的再生。在本研究中，我们从人MKN45胃癌细胞系的条件培养基中纯化了HGF激活剂的抑制剂，并分子克隆了其cDNA。 cDNA 序列显示该抑制剂具有两个明确的 Kunitz 结构域，表明该抑制剂是丝氨酸蛋白酶抑制剂 Kunitz 家族的成员。序列还显示抑制剂的初级翻译产物在COOH末端区域具有疏水序列。在MKN45细胞的膜部分以及条件培养基中检测到对HGF激活剂的抑制活性。这些结果表明，抑制剂可能以膜相关形式产生，并以蛋白水解截短的形式由生产细胞分泌。
Hepatocyte growth factor (HGF) activator is a serine protease that is produced and secreted by the liver and circulates in the blood as an inactive zymogen. In response to tissue injury, the HGF activator zymogen is converted to the active form by limited proteolysis. The activated HGF activator converts an inactive single chain precursor of HGF to a biologically active heterodimer in injured tissue, The activated HGF may be involved in the regeneration of the injured tissue, In this study, we purified an inhibitor of HGF activator from the conditioned medium of a human MKN45 stomach carcinoma cell line and molecularly cloned its cDNA. The sequence of the cDNA revealed that the inhibitor has two well defined Kunitz domains, suggesting that the inhibitor is a member of the Kunitz family of serine protease inhibitors. The sequence also showed that the primary translation product of the inhibitor has a hydrophobic sequence at the COOH-terminal region, Inhibitory activity toward HGF activator was detected in the membrane fraction as well as in the conditioned medium of MKN45 cells. These results suggest that the inhibitor may be produced as a membrane-associated form and secreted by the producing cells as a proteolytically truncated form.