Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis

Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis
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DOI:
10.1042/0264-6021:3460603
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发表时间:
2000-03-15
影响因子:
4.1
通讯作者:
Koh, GY
Koh, GY
中科院分区:
生物学3区
文献类型:
--
作者:
Kim, I;Kim, HG;Koh, GY

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利用退化PCR技术,我们从人和小鼠胚胎cDNA中分离出一种编码406和410个氨基酸的新蛋白的cDNA,并将其命名为“肝纤维蛋白原/血管生成素相关蛋白”(HFARP)。HFARP的n端和c端部分包含在血管生成素中保守的特征卷曲结构域和纤维蛋白原样结构域。在人和小鼠组织中,HFARP mRNA在肝脏中特异性表达。HFARP mRNA和蛋白主要存在于肝细胞中。HFARP在n端有一个高度疏水区域,这是一个典型的分泌信号序列和一个一致的糖基化位点。重组HFARP在COS-7细胞中分泌并糖基化。HFARP蛋白不仅存在于肝细胞中,也存在于循环血液中。重组HFARP作为血管内皮细胞的凋亡存活因子,但不结合Tie1或Tie2(内皮细胞酪氨酸激酶受体)。提示HFARP可能通过内分泌作用对内皮细胞发挥保护作用。
Using degenerate PCR we isolated a cDNA encoding a novel 406- and 410-amino acid protein from human and mouse embryonic cDNAs and have designated it 'hepatic fibrinogen/ angiopoietin-related protein' (HFARP). The N-terminal and C-terminal portions of HFARP contain the characteristic coiled-coil domains and fibrinogen-like domains that are conserved in angiopoietins. In human and mouse tissues, HFARP mRNA is specifically expressed in the liver. HFARP mRNA and protein are mainly present in the hepatocytes. HFARP has a highly hydrophobic region at the N-terminus that is typical of a secretory signal sequence and one consensus glycosylation site. Recombinant HFARP expressed in COS-7 cells is secreted and glycosylated. HFARP protein is present not only in the hepatocytes, but also in the circulating blood. Recombinant HFARP acts as an apoptosis survival factor for vascular endothelial cells, but does not bind to Tie1 or Tie2 (endothelial-cell tyrosine kinase receptors). These results suggest that HFARP may exert a protective function on endothelial cells through an endocrine action.