Antiplasmin Activity of a Peptide That Binds to the Receptor-binding Site of Angiogenin*
Antiplasmin Activity of a Peptide That Binds to the Receptor-binding Site of Angiogenin*
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与血管生成素受体结合位点结合的肽的抗纤溶酶活性*
DOI：
10.1074/jbc.m105526200
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
C. Chae
中科院分区：
文献类型：
--
作者：
Y. Gho;W. Yoon;C. Chae
已经提出血管生成素结合存在于内皮细胞表面上的肌动蛋白样分子。肌动蛋白抑制纤溶酶活性，但血管生成素-肌动蛋白复合物不具有活性。在这份报告中，我们发现纤溶酶抑制血管生成素和肌动蛋白之间的相互作用，这表明血管生成素和纤溶酶可能结合到肌动蛋白上的类似位点。在这里，我们报告说，chANG，抗血管生成素肽，结合到肌动蛋白结合位点的血管生成素，抑制纤溶酶的蛋白水解活性，而没有任何明显的影响纤溶酶原激活剂和基质金属蛋白酶的活动。其抗纤溶酶活性与肌动蛋白相当。chANG通过其与纤溶酶kringle结构域的结合抑制纤溶酶活性，而乱序chANG不与纤溶酶结合。ChANG还抑制分泌血管生成素的人纤维肉瘤和结肠直肠癌细胞的侵袭而不影响迁移。此外，chANG阻断纤维肉瘤细胞诱导的血管生成和结直肠癌细胞向肝脏的转移。因此，11-氨基酸肽chANG具有抗血管生成素和抗纤溶酶活性，并且可用于开发抗癌剂。
It has been suggested that angiogenin binds to an actin-like molecule present on the surface of endothelial cells. Actin inhibits plasmin activity, but the angiogenin-actin complex is not active. In this report, we found that plasmin inhibits the interaction between angiogenin and actin suggesting a possibility that both angiogenin and plasmin may bind to a similar site on actin. Here we report that chANG, an antiangiogenin peptide that binds to the actin-binding site of angiogenin, inhibits the proteolytic activity of plasmin without any apparent effect on the activities of plasminogen activators and matrix metalloproteases. Its antiplasmin activity is comparable with that of actin. chANG inhibits plasmin activity via its binding to plasmin kringle domains while scrambled chANG does not bind to plasmin. chANG also inhibits the invasion of angiogenin-secreting human fibrosarcoma and colorectal carcinoma cells without effecting migration. Furthermore, chANG blocks angiogenesis induced by fibrosarcoma cells and metastasis of colorectal carcinoma cells to the liver. Therefore, the 11-amino acid peptide chANG has both antiangiogenin and antiplasmin activity, and could be useful in the development of anticancer agents.
影响因子：
15.9
作者：
BRESALIER, RS;NIV, Y;KIM, YS
通讯作者：
KIM, YS