Synergistic assembly of linker for activation of T cells signaling protein complexes in T cell plasma membrane domains
Synergistic assembly of linker for activation of T cells signaling protein complexes in T cell plasma membrane domains
复制标题
DOI：
10.1074/jbc.m301212200
复制
发表时间：
2003-05-30
影响因子：
4.8
通讯作者：
Harder, T
中科院分区：
文献类型：
--
作者：
Hartgroves, LC;Lin, J;Harder, T
跨膜接头分子LAT （T细胞活化连接物）为信号蛋白复合物形成中心支架，这些蛋白复合物积聚在活化的T细胞抗原受体（TCR）附近。本研究采用免疫分离质膜结构域的生化分析和绿色荧光蛋白标记信号蛋白的荧光成像来研究LAT的不同酪氨酸基信号蛋白对接位点对TCR膜结构域LAT信号蛋白组装的贡献。我们发现LAT的磷脂酶C γ对接位点和不同的Grb2/Gads对接位点以相互依赖的方式发挥作用，并协同作用，在TCR信号组合中积累LAT、Grb2和磷脂酶C γ。二维凝胶显示，在分离的LAT信号复合物中，Grb2是主要的细胞质接头，而Gads、Crk-1和Grap的含量较低。综上所述，我们的数据表明了多分子TCR的协同组装。T细胞细胞膜结构域的LAT信号转导复合物。
Transmembrane adaptor molecule LAT ( linker for activation of T cells) forms a central scaffold for signaling protein complexes that accumulate in the vicinity of activated T cell antigen receptors (TCR). Here we used biochemical analysis of immunoisolated plasma membrane domains and fluorescence imaging of green fluorescence protein-tagged signaling proteins to investigate the contributions of different tyrosine-based signaling protein docking sites of LAT to the formation of LAT signaling protein assemblies in TCR membrane domains. We found that the phospholipase C gamma docking site of LAT and different Grb2/Gads docking sites function in an interdependent fashion and synergize to accumulate LAT, Grb2, and phospholipase C gamma in TCR signaling assemblies. Two-dimensional gels showed that Grb2 is a predominant cytoplasmic adaptor in the isolated LAT signaling complexes, whereas Gads, Crk-1, and Grap are present in lower amounts. Taken together our data suggest a synergistic assembly of multimolecular TCR . LAT signal transduction complexes in T cell plasma membrane domains.