Essential role for IKKγ/NEMO in TCR-induced IL-2 expression in Jurkat T cells
Essential role for IKKγ/NEMO in TCR-induced IL-2 expression in Jurkat T cells
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DOI：
10.1002/eji.200323650
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发表时间：
2003-07-01
影响因子：
5.4
通讯作者：
Ting, AT
中科院分区：
文献类型：
--
作者：
He, KL;Ting, AT
T细胞中IL-2基因的表达受多种转录因子的调控，但NF-κ B信号通路在TCR依赖性IL-2产生中的作用仍不清楚。在这项研究中，我们使用体细胞遗传学方法来解决这个问题。在缺乏IKK γ/NEMO的突变型Jurkat T细胞中触发TCR不能诱导IL-2，这是由于I-KB激酶活性、I-KB α降解和NF-κ B DNA结合活性的选择性丧失。野生型和突变型T细胞之间的IL-2启动子中的AP-1和NF-AT结合活性相当。通过重新引入外源性IKK γ挽救了突变细胞系中的这些缺陷。综上所述，我们的数据表明IKK γ在TCR诱导的IL-2表达的信号通路中起着重要作用。
The control of IL-2 gene expression in T cells by multiple transcriptional factors has been extensively explored, however, the role of the NF-KB signaling pathway in TCR-dependent IL-2 production still remains unclear. In this study, we used a somatic cell genetics approach to address this question. Triggering TCR in mutant Jurkat T cells lacking IKKgamma/NEMO failed to induce IL-2 due to a selective loss in I-KB kinase activity, I-KBalpha degradation and NF-KB DNA-binding activity. The AP-1 and NF-AT binding activities in the IL-2 promoter were comparable between wild-type and mutant T cells. These defects in the mutant cell line were rescued by the reintroduction of exogenous IKKgamma. Taken together, our data demonstrate that IKKgamma plays an essential role in TCR-induced signaling pathways leading to IL-2 expression.