Kimura T, Hisano M, Inoue Y, Adachi M
The First Department of Internal Medicine, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, 142-8666, Tokyo, Japan.
Immunol Lett. 2001 Jan 1;75(2):123-9. doi: 10.1016/s0165-2478(00)00295-9.
Aggregation of the high affinity IgE receptors (FcepsilonRI) on basophils and mast cells, members of the immune receptor family, initiates a cascade of events that results in the release of inflammatory mediators. This pathway involves the activation of several protein-tyrosine kinases, including Lyn, Syk, Btk, and Fak that induce the tyrosine phosphorylation of various proteins. The linker for activation of T cells (LAT), was originally found as a ZAP-70 tyrosine kinase substrate that linked T cell receptors to cellular activation, and was expressed in T cells, NK cells and mast cells. Here we show that LAT expressed in the RBL-2H3 rat mast cell line is tyrosine-phosphorylated after aggregation of FcepsilonRI. The tyrosine phosphorylation of the LAT was dramatically enhanced after receptor aggregation. Furthermore, a tyrosine-phosphorylated 80-kDa protein associated with LAT transiently after receptor aggregation. GST fusion proteins containing parts of PLCgamma or PI3 kinase can bind LAT. These results suggest that LAT plays an important role not only in T cell, but also in mast cell activation, and that the association among these signaling molecules is critical for FcepsilonRI-mediated intracellular signal transduction in mast cells.
嗜碱性粒细胞和肥大细胞上的高亲和力IgE受体（FcepsilonRI）聚集，免疫受体家族的成员引发一系列导致炎症介质释放的事件。此途径涉及多种蛋白酪氨酸激酶的激活，包括Lyn、Syk、Btk和Fak，它们诱导各种蛋白质的酪氨酸磷酸化。T细胞激活连接蛋白（LAT）最初作为将T细胞受体与细胞激活联系起来的ZAP-70酪氨酸激酶底物被发现，并在T细胞、NK细胞和肥大细胞中表达。在此我们表明，在RBL-2H3大鼠肥大细胞系中表达的LAT在FcepsilonRI聚集后发生酪氨酸磷酸化。受体聚集后，LAT的酪氨酸磷酸化显著增强。此外，受体聚集后，一种与LAT相关的酪氨酸磷酸化80 kDa蛋白短暂出现。含有部分PLCγ或PI3激酶的GST融合蛋白可结合LAT。这些结果表明，LAT不仅在T细胞中，而且在肥大细胞激活中发挥重要作用，并且这些信号分子之间的关联对于肥大细胞中FcepsilonRI介导的细胞内信号转导至关重要。
