TCR signaling to NF-κB and mTORC1: Expanding roles of the CARMA1 complex.
TCR signaling to NF-κB and mTORC1: Expanding roles of the CARMA1 complex.
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DOI：
10.1016/j.molimm.2015.07.024
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发表时间：
2015-12
影响因子：
3.6
通讯作者：
Sun SC
中科院分区：
文献类型：
--
作者：
Shi JH;Sun SC
Naïve t细胞激活需要来自t细胞受体（TCR）和共刺激分子CD28的信号。TCR和CD28信号的中心介质是支架蛋白CARMA1，它通过与伴侣蛋白Bcl10和MALT1形成复合物而起作用。CARMA1信号复合体的一个众所周知的功能是介导i -κB激酶（IKK）及其靶转录因子NF-κB的激活，从而促进t细胞的活化和存活。最近的证据表明，CARMA1还介导TCR/ cd28刺激的ikk相关激酶TBK1的激活，TBK1在调节T细胞的稳态和迁移中起作用。此外，CARMA1复合体将TCR/CD28信号连接到mTORC1的激活，mTORC1是一种调节t细胞功能各个方面的代谢激酶。本文将讨论carma1依赖性信号通路的激活机制及其在调节t细胞功能中的作用。
Naïve T-cell activation requires signals from both the T-cell receptor (TCR) and the costimulatory molecule CD28. A central mediator of the TCR and CD28 signals is the scaffold protein CARMA1, which functions by forming a complex with partner proteins, Bcl10 and MALT1. A well-known function of the CARMA1 signaling complex is to mediate activation of IκB kinase (IKK) and its target transcription factor NF-κB, thereby promoting T-cell activation and survival. Recent evidence suggests that CARMA1 also mediates TCR/CD28-stimulated activation of the IKK-related kinase TBK1, which plays a role in regulating the homeostasis and migration of T cells. Moreover, the CARMA1 complex connects the TCR/CD28 signals to the activation of mTORC1, a metabolic kinase regulating various aspects of T-cell functions. This review will discuss the mechanism underlying the activation of the CARMA1-dependent signaling pathways and their roles in regulating T-cell functions.