T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10.
T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10.
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T 细胞中 mTOR 信号传导的 T 细胞受体依赖性激活是由 Carma1 和 MALT1 介导的，但不是 Bcl10。
DOI：
10.1126/scisignal.2005169
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发表时间：
2014-06-10
影响因子：
7.3
通讯作者：
Kane LP
中科院分区：
文献类型：
--
作者：
Hamilton KS;Phong B;Corey C;Cheng J;Gorentla B;Zhong X;Shiva S;Kane LP
向雷帕霉素 (mTOR) 机制靶点发出信号可调节多种细胞过程，包括蛋白质翻译、细胞增殖、代谢和自噬。这些效应部分由 mTOR 靶标 S6 激酶 (S6K) 和真核起始因子 4E (eIF4E) 结合蛋白 1 (4E-BP1) 介导。大多数模型将 Akt 置于研究最充分的 mTOR 复合体 mTORC1 的上游；然而，研究质疑 Akt 是否是该通路所必需的，至少在 T 细胞中是这样。我们发现，接头蛋白 Carma1 [含有半胱天冬酶募集结构域 (CARD) 的膜相关蛋白 1 (Carma1)] 及其至少一种相关蛋白，副半胱天冬酶 MALT1（粘膜相关淋巴组织淋巴瘤易位蛋白 1），是 T 细胞中 mTOR 最佳激活所必需的，以响应 T 细胞受体 (TCR) 和辅助受体 CD28 的刺激。然而，TCR 依赖性 mTOR 通路激活不需要 Carma1 和 MALT1 的另一个常见结合伴侣 Bcl10。与这些发现一致，MALT1 活性是 CD4+ T 细胞增殖所必需的，但早期 TCR 依赖性激活事件则不需要。与对 mTOR 的影响也一致，MALT1 活性是增加活化 CD4+ T 细胞代谢通量所必需的。总之，我们的数据表明，Carma1 和 MALT1 在 TCR 参与后激活 T 细胞中 mTOR 信号传导过程中发挥着以前未被认识到的作用。
Signaling to the mechanistic target of rapamycin (mTOR) regulates diverse cellular processes, including protein translation, cellular proliferation, metabolism, and autophagy. These effects are mediated in part by the mTOR targets S6 kinase (S6K) and eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). Most models place Akt upstream of the best-studied mTOR complex, mTORC1; however, studies have called into question whether Akt is necessary for this pathway, at least in T cells. We found that the adaptor protein Carma1 [caspase recruitment domain (CARD)-containing membrane-associated protein 1 (Carma1)] and at least one of its associated proteins, the paracaspase MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), were required for optimal activation of mTOR in T cells in response to stimulation of the T cell receptor (TCR) and the coreceptor CD28. However, another common binding partner of Carma1 and MALT1, Bcl10, was not required for TCR-dependent activation of the mTOR pathway. Consistent with these findings, MALT1 activity was required for the proliferation of CD4+ T cells, but not early TCR-dependent activation events. Also consistent with an effect on mTOR, MALT1 activity was required for the increased metabolic flux in activated CD4+ T cells. Together, our data suggest that Carma1 and MALT1 play previously unappreciated roles in the activation of mTOR signaling in T cells after engagement of the TCR.
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影响因子：
16
作者：
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通讯作者：
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