论文摘要
肝细胞生长因子激活因子抑制因子1（hepatocyte growth factor activator inhibitor type 1,HAI-1）是一种由上皮细胞分泌的Kunitz型丝氨酸蛋白酶抑制因子。HAI-1首先以跨膜蛋白形式产生,其胞外片段含两个Kunitz功能域,当膜型HAI-1的胞外区从膜上脱落时可形成两种主要的分泌型HAI-1,一种含一个Kunitz功能域,另一种含两个Kunitz功能域。HAI-1能有效地抑制肝细胞生长因子激活因子（hepatocyte growth factor activator,HGFA）和Ⅱ型丝氨酸蛋白酶matriptase的活性。肝细胞生长因子（hepatocyte growth factor,HGF）又称为扩散因子（scatter factor,SF）,是一种与细胞的增殖和运动密切相关的因子,其受体为c-met基因产物。HGF/SF以无活性的前体形式由间质细胞分泌,然后被HGFA或matriptase水解激活,从而触发HGF/c-Met这一在受损组织再生和肿瘤细胞侵袭性生长中均扮演重要角色的信号传导途径。研究表明HAI-1不仪是HGFA的抑制因子,也是有活性的HGFA的特异性结合蛋白,能够在在细胞表面富集HGFA,这可能和在组织损伤和发炎等情况下维持局部HGFA的浓度有关。推测HAI-1可能通过调节HGFA和matriptase的活性、进而影响HGF的激活来参与HGF/c-Met这一信号传导途径的调控。matriptase是HAI-1作用的另一个重要蛋白酶,能活化HGF/SF和尿激酶型血纤维蛋白溶酶原激活因子（urokinase-type plasminogen activator,uPA）——这两种蛋白都被认为与癌细胞生长和运动相关,而matriptase在多种癌细胞中有表达增强的现象。因此HAI-1可能通过调控matriptase而在肿瘤的进展中起重要的作用。 HGF/SF的激活在HGF/SF诱导的信号途径中是关键性的步骤,而目前人们对HGFA、matriptase等HGF/SF激活相关因子的调控仍然所知不多,因此对HAI-1等上游活性调控因子进行研究有着十分重要的意义。为了解HAI-1对肿瘤细胞的生长和转
论文目录
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