Tissue-type plasminogen activator is a target of the tumor suppressor gene maspin
Tissue-type plasminogen activator is a target of the tumor suppressor gene maspin
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DOI：
10.1073/pnas.95.2.499
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发表时间：
1998-01-20
影响因子：
11.1
通讯作者：
Sager, R
中科院分区：
文献类型：
--
作者：
Sheng, SJ;Truong, B;Sager, R
maspin蛋白在乳腺癌和前列腺癌中具有肿瘤抑制活性。Maspin在结构上属于丝氨酸蛋白酶抑制剂（serine protease inhibitors，Serpin）超家族成员，但与经典的Serpin有一定的差异。我们发现单链组织型纤溶酶原激活剂（single chain tissue plasminogen activator，sctPA）能特异性地与maspin反应位点环肽相互作用，并与重组maspin [rMaspin（i）]形成稳定的复合物。观察到rMaspin（i）对sctPA激活纤溶酶原的主要作用，首先，rMaspin（i）激活游离的sctPA，其次，它抑制由聚-D-赖氨酸预激活的sctPA。第三，rMaspin（i）对纤维蛋白原/明胶预活化的sctPA活性产生双相效应，在低浓度下作为竞争性抑制剂（
The maspin protein has tumor suppressor activity in breast and prostate cancers. It inhibits cell motility and invasion in vitro and tumor growth and metastasis in nude mice, Maspin is structurally a member of the serpin (serine protease inhibitors) superfamily but deviates somewhat from classical serpins, We find that single-chain tissue plasminogen activator (sctPA) specifically interacts with the maspin reactive site loop peptide and forms a stable complex with recombinant maspin [rMaspin(i)]. Major effects of rMaspin(i) are observed on plasminogen activation by sctPA, First, rMaspin(i) activates free sctPA, Second, it inhibits sctPA preactivated by poly-D-lysine. Third, rMaspin(i) exerts a biphasic effect on the activity of sctPA preactivated by fibrinogen/gelatin, acting as a competitive inhibitor at low concentrations (