T cell development involves TRAF3IP3-mediated ERK signaling in the Golgi.
T cell development involves TRAF3IP3-mediated ERK signaling in the Golgi.
复制标题
DOI：
10.1084/jem.20150110
复制
发表时间：
2015-07-27
期刊：
影响因子：
--
通讯作者：
Sun SC
中科院分区：
文献类型：
--
作者：
Zou Q;Jin J;Xiao Y;Hu H;Zhou X;Jie Z;Xie X;Li JY;Cheng X;Sun SC
Zou等鉴定了一种高尔基体相关因子TRAF 3相互作用蛋白3（TRAF 3 IP 3），作为胸腺细胞发育的关键介质，调节高尔基体中TCR刺激的ERK信号传导。胸腺中T淋巴细胞的产生是由T细胞受体（TCR）的信号转导引导的，但其潜在机制尚不完全清楚。在这里，我们已经确定了高尔基体相关因子，TRAF 3相互作用蛋白3（TRAF 3 IP 3），作为胸腺细胞发育的重要介质。小鼠TRAF 3 IP 3缺陷减弱了由受损胸腺细胞阳性选择引起的成熟胸腺细胞的产生。TRAF 3 IP 3介导TCR刺激的促分裂原活化蛋白激酶（MAPK）细胞外信号调节激酶（ERK）及其上游激酶促分裂原/细胞外信号调节激酶（MEK）的活化。有趣的是，TRAF 3 IP 3通过将MEK募集到高尔基体来发挥这种信号传导功能，从而促进MEK与其激活剂BRAF的相互作用。组成型活性MEK的转基因表达拯救Traf 3 ip 3敲除小鼠中的T细胞发育阻滞这些发现确立了TRAF 3 IP 3作为T细胞发育的新调节因子，并表明调节胸腺细胞发育的高尔基体特异性ERK信号传导机制。
Zou et al. identify a Golgi-associated factor, TRAF3-interacting protein 3 (TRAF3IP3), as a crucial mediator of thymocyte development regulating TCR-stimulated ERK signaling in the Golgi. Generation of T lymphocytes in the thymus is guided by signal transduction from the T cell receptor (TCR), but the underlying mechanism is incompletely understood. Here we have identified a Golgi-associated factor, TRAF3-interacting protein 3 (TRAF3IP3), as a crucial mediator of thymocyte development. TRAF3IP3 deficiency in mice attenuates the generation of mature thymocytes caused by impaired thymocyte-positive selection. TRAF3IP3 mediates TCR-stimulated activation of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) and its upstream kinase mitogen/extracellular signal-regulated kinase (MEK). Interestingly, TRAF3IP3 exerts this signaling function through recruiting MEK to the Golgi and, thereby, facilitating the interaction of MEK with its activator BRAF. Transgenic expression of a constitutively active MEK rescues the T cell development block in Traf3ip3 knockout mice. These findings establish TRAF3IP3 as a novel regulator of T cell development and suggest a Golgi-specific ERK signaling mechanism that regulates thymocyte development.