Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR
Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR
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DOI：
10.1016/s0960-9822(99)80093-1
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发表时间：
1999-02-25
期刊：
影响因子：
9.2
通讯作者：
Ashkenazi, A
中科院分区：
文献类型：
--
作者：
Gurney, AL;Marsters, SA;Ashkenazi, A
肿瘤坏死因子（TNF）和TNF受体（TNFR）基因超家族调节多种生物学功能。包括细胞增殖、分化和存活[1-3]。我们已经鉴定了一种新的 TNF 相关配体，称为人 GITR 配体 (hGITRL) 及其人受体 (hGITR)，后者是最近发现的鼠糖皮质激素诱导的 TNFR 相关 (mGITR) 蛋白的直系同源物 [4]。 hGITRL 基因定位于染色体 1q23，靠近 TNF 同系物 Fas/CD95 配体的基因 [5]，hGITR 基因定位于染色体 1p36，靠近编码 TNFR 同系物的五个基因簇 [1,6]。我们在几种外周组织中发现了 hGITRL mRNA，并在培养的血管内皮细胞上检测到了 hGITRL 蛋白。组织中 hGITR mRNA 水平普遍较低；然而，在外周血 T 细胞中，抗原受体刺激导致 hGITR 转录物的大量诱导。在胚胎肾 293 细胞中共转染 hGITRL 和 hGITR 可通过一条似乎涉及 TNFR 相关因子 2 (TRAF2) [7] 和 NF-kappa B 诱导激酶 (NIK) [8] 的途径激活抗凋亡转录因子 NF-kappa B。 Jurkat T 白血病细胞中 hGITRL 和 hGITR 的共转染抑制了抗原受体诱导的细胞死亡。因此，hGITRL和hGITR可能调节外周组织中T淋巴细胞的存活。
The tumor necrosis factor (TNF) and TNF receptor (TNFR) gene superfamilies regulate diverse biological functions,. including cell proliferation, differentiation, and survival [1-3]. We have identified a new TNF-related ligand, designated human GITR ligand (hGITRL), and its human receptor (hGITR), an ortholog of the recently discovered murine glucocorticoid induced TNFR-related (mGITR) protein [4]. The hGITRL gene mapped to chromosome 1q23, near the gene for the TNF homolog Fas/CD95 ligand [5], The hGITR gene mapped to chromosome 1p36, near a cluster of five genes encoding TNFR homologs [1,6]. We found hGITRL mRNA in several peripheral tissues, and detected hGITRL protein on cultured vascular endothelial cells. The levels of hGITR mRNA in tissues were generally low; in peripheral blood T cells, however, antigen receptor stimulation led to a substantial induction of hGITR transcripts. Cotransfection of hGITRL and hGITR in embryonic kidney 293 cells activated the anti-apoptotic transcription factor NF-kappa B, via a pathway that appeared to involve TNFR associated factor 2 (TRAF2) [7] and NF-kappa B-inducing kinase (NIK) [8]. Cotransfection of hGITRL and hGITR in Jurkat T leukemia cells inhibited antigen-receptor-induced cell death. Thus, hGITRL and hGITR may modulate T lymphocyte survival in peripheral tissues.