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.

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受调节信号通路的诱导。一种关键的 TCR 诱导信号蛋白是接头蛋白 LAT。在 TCR 刺激后，LAT 在保守的酪氨酸上被磷酸化，这有助于形成信号通路传播所需的多蛋白复合物。尽管已经研究了保守酪氨酸在 LAT 介导的信号传导中的作用，但很少有研究检查 LAT 较大区域在 TCR 诱导通路中的作用。在这项研究中，97 种哺乳动物 LAT 蛋白的序列比对用于鉴定 LAT 上的几个“功能”结构域。使用在 Jurkat E6.1 细胞中表达的 LAT 突变体，我们观察到 LAT 的膜近端、富含脯氨酸的区域和包含保守酪氨酸的域的正确顺序对于最佳 TCR 介导的早期信号、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，这些区域的存在和正确的顺序是 TCR 介导的信号通路传播所必需的。