Negative feedback loop in T-cell activation through MAPK-catalyzed threonine phosphorylation of LAT
Negative feedback loop in T-cell activation through MAPK-catalyzed threonine phosphorylation of LAT
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DOI：
10.1038/sj.emboj.7600268
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发表时间：
2004-07-07
期刊：
影响因子：
11.4
通讯作者：
Koyasu, S
中科院分区：
文献类型：
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作者：
Matsuda, S;Miwa, Y;Koyasu, S
丝裂原活化蛋白激酶（MAPK）级联参与多种细胞反应，包括增殖、分化和凋亡。我们已经开发了一种表达筛选方法来检测体内底物的MAPK在哺乳动物细胞中，并确定了膜蛋白，接头活化T细胞（LAT），作为MAPK的目标。LAT是T细胞信号传导所必需的衔接蛋白，在其Thr 155处被ERK磷酸化以响应T细胞受体刺激。Thr 155磷酸化降低了LAT募集PLC γ 1和SLP76的能力，导致随后下游事件的减弱，例如[Ca2+]（i）ERK途径的动员和激活。我们的数据揭示了一个新的作用MAPKs在负反馈回路中的T细胞活化通过苏氨酸磷酸化的LAT。
Mitogen-activated protein kinase (MAPK) cascades are involved in a variety of cellular responses including proliferation, differentiation, and apoptosis. We have developed an expression screening method to detect in vivo substrates of MAPKs in mammalian cells, and identified a membrane protein, linker for activation of T cells (LAT), as an MAPK target. LAT, an adapter protein essential for T-cell signaling, is phosphorylated at its Thr 155 by ERK in response to T-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of LAT to recruit PLCgamma1 and SLP76, leading to attenuation of subsequent downstream events such as [Ca2+](i) mobilization and activation of the ERK pathway. Our data reveal a new role for MAPKs in a negative feedback loop in T-cell activation via threonine phosphorylation of LAT.