Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth
Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth
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DOI：
10.1074/jbc.272.36.22924
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发表时间：
1997-09-05
影响因子：
4.8
通讯作者：
Llinas, M
中科院分区：
文献类型：
--
作者：
Cao, YH;Chen, A;Llinas, M
血管抑素是一种有效的血管生成抑制物，已被确认为纤溶酶原的内部片段，包括其前四个kringle模块。我们最近已经证明，血管抑素的抗内皮细胞增殖活性也表现在纤溶酶原的前三个kringle结构上，而kringle 4(CaO，Y.，Ji，R.-W.，Davidson，D.，Schaller，J.，Marti，D.，Sohndel，S.，McCance，S.G.，O‘Reilly，M.S.，Llinas，M.和Folkman，J.(1996)J.Biol)也显示出抗内皮细胞增殖的活性。化学。271、29461-29467)。我们现在报道，人纤溶酶原的kringle5片段是内皮细胞增殖的特异性抑制物。人纤溶酶原蛋白水解物Kringle5对牛毛细血管内皮细胞有较强的抑制作用，半数抑制浓度(ED50)约为50 nM。因此，在抑制碱性成纤维细胞生长因子刺激的毛细血管内皮细胞增殖方面，Kringle5似乎比Angiostatin更有效。在大肠杆菌中表达的适当折叠的重组小鼠kringle5蛋白，显示出与蛋白水解性kringle5片段类似的抑制作用。因此，人纤溶酶原的Kringle5结构域是一种新型的内皮抑制物，足以阻断生长因子刺激的内皮细胞生长。
Angiostatin is a potent angiogenesis inhibitor which has been identified as an internal fragment of plasminogen that includes its first four kringle modules. We have recently demonstrated that the anti-endothelial cell proliferative activity of angiostatin is also displayed by the first three kringle structures of plasminogen and marginally so by kringle 4 (Cao, Y., Ji, R.-W., Davidson, D., Schaller, J., Marti, D., Sohndel, S., McCance, S. G., O'Reilly, M. S., Llinas, M., and Folkman, J. (1996) J. Biol. Chem. 271, 29461-29467). We now report that the kringle 5 fragment of human plasminogen is a specific inhibitor for endothelial cell proliferation. Kringle 5 obtained as a proteolytic fragment of human plasminogen displays potent inhibitory effect on bovine capillary endothelial cells with a half-maximal concentration (ED50) of approximately 50 nM. Thus, kringle 5 would appear to be more potent than angiostatin on inhibition of basic fibroblast growth factor-stimulated capillary endothelial cell proliferation. Appropriately folded recombinant mouse kringle 5 protein, expressed in Escherichia coli, exhibits a comparable inhibitory effect as the proteolytic kringle 5 fragment. Thus, kringle 5 domain of human plasminogen is a novel endothelial inhibitor that is sufficiently potent to block the growth factor-stimulated endothelial cell growth.