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The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions

机译：TCR介导的信号传导和下游功能需要膜近端脯氨酸富含脯氨酸区域和正确顺序的C-末端酪氨酸顺序

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摘要

The primary activating receptor for T cells is the T cell receptor (TCR), which is stimulated upon binding to an antigen/MHC complex. TCR activation results in the induction of regulated signaling pathways vital for T cell differentiation, cellular adhesion and cytokine release. A critical TCR-induced signaling protein is the adaptor protein LAT. Upon TCR stimulation, LAT is phosphorylated on conserved tyrosines, which facilitates the formation of multiprotein complexes needed for propagation of signaling pathways. Although the role of the conserved tyrosines in LAT-mediated signaling has been investigated, few studies have examined the role of larger regions of LAT in TCR-induced pathways. In this study, a sequence alignment of 97 mammalian LAT proteins was used to identify several "functional" domains on LAT. Using LAT mutants expressed in Jurkat E6.1 cells, we observed that the membrane proximal, proline-rich region of LAT and the correct order of domains containing conserved tyrosines are necessary for optimal TCR-mediated early signaling, cytokine production, and cellular adhesion. Together, these data show that LAT contains distinct regions whose presence and correct order are required for the propagation of TCR-mediated signaling pathways.
机译：T细胞的主要激活受体是T细胞受体（TCR），它在与抗原/MHC复合物结合时受到刺激。TCR激活导致对T细胞分化、细胞粘附和细胞因子释放至关重要的调节信号通路的诱导。TCR诱导的一个关键信号蛋白是衔接蛋白LAT。在TCR刺激下，LAT在保守的酪氨酸上磷酸化，这有助于形成信号通路传播所需的多蛋白复合物。尽管保守的酪氨酸在LAT介导的信号传导中的作用已经被研究，但很少有研究检测LAT的较大区域在TCR诱导的通路中的作用。在这项研究中，97个哺乳动物LAT蛋白的序列比对被用于鉴定LAT上的几个“功能”域。使用Jurkat E6中表达的LAT突变体。1细胞中，我们观察到，LAT膜近端富含脯氨酸的区域以及含有保守酪氨酸的正确序列对于最佳TCR介导的早期信号传导、细胞因子产生和细胞粘附是必要的。总之，这些数据表明LAT包含不同的区域，其存在和正确的顺序是TCR介导的信号通路传播所必需的。

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