Factor XII-dependent Contact Activation on Endothelial Cells and Binding Proteins gC1qR and Cytokeratin 1

Factor XII-dependent Contact Activation on Endothelial Cells and Binding Proteins gC1qR and Cytokeratin 1
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内皮细胞和结合蛋白 gC1qR 和细胞角蛋白 1 上的因子 XII 依赖性接触激活

DOI:
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发表时间:
2001
影响因子:
6.7
通讯作者:
A. Kaplan
A. Kaplan
中科院分区:
医学2区
文献类型:
--
作者:
K. Joseph;Y. Shibayama;B. Ghebrehiwet;A. Kaplan

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虽然激肽形成途径的蛋白质沿着内皮细胞表面结合,但这种蛋白水解级联的激活机制尚不清楚。内皮细胞表面蛋白gC1qR和细胞角蛋白1能够在锌依赖性反应中结合因子XII和高分子量激肽原(HK),因此我们认为这些蛋白可能催化级联反应的启动。因子XII、前激肽释放酶和HK与gC1qR或细胞角蛋白1的孵育导致前激肽释放酶向激肽释放酶的锌依赖性和因子XII依赖性转化。我们还证明,正常血浆能够激活后与细胞的相互作用,而血浆缺乏因子XII,前激肽释放酶和HK不激活。正常的血浆激活是可重复的抗体gC1qR和细胞角蛋白1。因此,gC1qR和细胞角蛋白1代表了激活血浆激肽形成级联反应的潜在起始表面,并且可能由于它们沿沿着细胞表面表达而这样做。
Summary Although proteins of the kinin-forming pathway are bound along the surface of endothelial cells, the mechanism of activation of this proteolytic cascade is unclear. Endothelial cell surface proteins, gC1qR and cytokeratin 1, are capable of binding Factor XII and high molecular weight kininogen (HK) in a zinc-dependent reaction thus we considered the possibility that these proteins might catalyze initiation of the cascade. Incubation of Factor XII, prekallikrein, and HK with gC1qR or cytokeratin 1 leads to a zinc-dependent and Factor XII-dependent conversion of prekallikrein to kallikrein. We also demonstrate that normal plasma is capable of activating upon interaction with the cells whereas plasma deficient in Factor XII, prekallikrein and HK do not activate. Normal plasma activation was inhibitable by antibody to gC1qR and cytokeratin 1. Thus, gC1qR and cytokeratin 1, represent potential initiating surfaces for activation of the plasma kinin-forming cascade and may do so as a result of their expression along cell surfaces.
DOI: 10.1073/pnas.95.7.3615
发表时间: 1998-03-31
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DOI: 10.1016/s0021-9258(18)89258-4
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发表时间: 1988-11
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影响因子: --
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高分子量激肽原肽抑制内皮细胞表面激肽释放酶的形成以及随后的尿激酶依赖性纤溶酶的形成。
DOI: --
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