Smad-dependent cooperative regulation of interleukin 2 receptor α chain gene expression by T cell receptor and transforming growth factor-β
Smad-dependent cooperative regulation of interleukin 2 receptor α chain gene expression by T cell receptor and transforming growth factor-β
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DOI：
10.1074/jbc.m505833200
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发表时间：
2005-10-07
影响因子：
4.8
通讯作者：
Leonard, WJ
中科院分区：
文献类型：
--
作者：
Kim, HP;Kim, BG;Leonard, WJ
白细胞介素2受体α链(IL-2Rα)是高亲和力IL-2受体的一个组成部分，因此对T细胞生长和其他淋巴功能具有重要的调节作用。5个正调控区域共同控制对抗原和IL-2的反应中谱系受限和激活依赖的IL-2Rα的诱导。我们现在发现，转化生长因子-β与T细胞受体(TCR)信号协同作用，增加IL-2Rα基因的表达。此外，我们确定了第六个正调控区域，它调节经抗CD3+抗CD28和转化生长因子-β处理的细胞中IL-2Rα的表达，并表明该区域包含SMAD3、AP-1和cAMP反应元件结合蛋白/ATF蛋白的结合位点。在Smad3(-/-)和Smad4(-/-)小鼠的CD4(+)T细胞中，转化生长因子-β对IL-2Rα的诱导作用减弱，表明Smad复合体的重要性。因此，我们在IL-2Rα基因中发现了一个新的正调节区，它介导了依赖于转化生长因子的基因的诱导。这些发现与激活的T细胞和调节性T细胞上IL-2Rα的表达有关。
The interleukin 2 receptor alpha chain (IL-2R alpha) is a component of high affinity IL-2 receptors and thus critically regulates T cell growth and other lymphoid functions. Five positive regulatory regions together control lineage-restricted and activation-dependent IL-2R alpha induction in response to antigen and IL-2. We now show that TGF-beta cooperates with T cell receptor (TCR) signaling to increase IL-2R alpha gene expression. Moreover, we identify a sixth positive regulatory region that regulates IL-2R alpha expression in cells treated with anti-CD3 + anti-CD28 as well as TGF-beta and show that this region contains binding sites for Smad3, AP-1, and cAMP-responsive element-binding protein/ ATF proteins. The importance of Smad complexes is indicated by impaired IL-2R alpha induction by TGF-beta in CD4(+) T cells from both Smad3(-/-) and Smad4(-/-) mice. Thus, we have identified a novel positive regulatory region in the IL-2R alpha gene that mediates TGF-beta-dependent induction of the gene. These findings have implications related to IL-2R alpha expression on activated T cells and regulatory T cells.