Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth

Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth
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DOI:
10.1074/jbc.273.42.27548
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发表时间:
1998-10-16
影响因子:
4.8
通讯作者:
Young, PR
Young, PR
中科院分区:
生物学2区
文献类型:
--
作者:
Harrop, JA;McDonnell, PC;Young, PR

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疱疹病毒进入介质(HVEM)是肿瘤坏死因子(TNF)受体家族的一员,在感染过程中介导疱疹病毒进入细胞。在过表达时,HVEM通过TNF受体相关因子(TRAF)介导的机制激活NF-κ B和AP-1。使用HVEM-Fc融合蛋白,我们筛选了来自表达序列fag数据库的新型TNF相关蛋白的可溶形式。其中之一,我们命名为HVEM-L,以44 nM的亲和力特异性结合HVEM-Fc。这种关联被证实与受体和配体的可溶性和膜形式,HVEM-L mRNA在脾,淋巴结,巨噬细胞和T细胞中表达,并编码240个氨基酸的蛋白质。该蛋白质的可溶性分泌形式在同种异体反应期间刺激T淋巴细胞增殖,抑制HT-29细胞生长,并弱刺激NF-κ B依赖性转录。
Herpesvirus entry mediator (HVEM), a member of the tumor necrosis factor (TNF) receptor family, mediates herpesvirus entry into cells during infection. Upon overexpression, HVEM activates NF-kappa B and AP-1 through a TNF receptor-associated factor (TRAF)-mediated mechanism. Using an HVEM-Fc fusion protein, we screened soluble forms of novel TNF-related proteins derived from an expressed sequence fag data base. One of these, which we designated HVEM-L, specifically bound to HVEM-Fc with an affinity of 44 nM. This association was confirmed with soluble and membrane forms of both receptor and ligand, HVEM-L mRNA is expressed in spleen, lymph nodes, macrophages, and T cells and encodes a 240-amino acid protein. A soluble, secreted form of the protein stimulates proliferation of T lymphocytes during allogeneic responses, inhibits HT-29 cell growth, and weakly stimulates NF-kappa B-dependent transcription.