Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction.
Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction.
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DOI：
10.1084/jem.190.10.1517
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发表时间：
1999-11-15
期刊：
影响因子：
--
通讯作者：
Singer A
中科院分区：
文献类型：
--
作者：
Bosselut R;Zhang W;Ashe JM;Kopacz JL;Samelson LE;Singer A
活化T细胞连接蛋白(LAT)是一种连接蛋白，其酪氨酸磷酸化是T细胞受体(TCR)信号转导的关键。后来的磷酸化是由蛋白酪氨酸激酶ZAP-70完成的，但完全不清楚LAT(与TCR无关)如何与ZAP-70(与TCR结合)相遇。在这里，我们表明LAT与表面的CD4和CD8辅助受体结合，并且它的结合受到介导LCK结合的相同辅助受体半胱氨酸基序的促进。事实上，LAT与Lck竞争结合单个辅受体分子，但与Lck的不同之处在于，LAT优先与CD8结合，而不是与CD4+CD8+胸腺细胞结合。重要的是，作为LAT与表面辅助受体结合的结果，TCR与表面辅助受体的共同作用诱导了LAT的磷酸化和下游信号介质对辅助受体相关的LAT分子的特异性募集。这些结果提示了CD4和CD8辅助受体在TCR信号转导中的一种新功能，即通过将LAT招募到主要组织相容性复合体参与的TCR复合体来促进ZAP-70对LAT的磷酸化。
Linker for activation of T cells (LAT) is an adaptor protein whose tyrosine phosphorylation is critical for transduction of the T cell receptor (TCR) signal. LAT phosphorylation is accomplished by the protein tyrosine kinase ZAP-70, but it is not at all clear how LAT (which is not associated with the TCR) encounters ZAP-70 (which is bound to the TCR). Here we show that LAT associates with surface CD4 and CD8 coreceptors and that its association is promoted by the same coreceptor cysteine motif that mediates Lck binding. In fact, LAT competes with Lck for binding to individual coreceptor molecules but differs from Lck in its preferential association with CD8 rather than CD4 in CD4+CD8+ thymocytes. Importantly, as a consequence of LAT association with surface coreceptors, coengagement of the TCR with surface coreceptors induces LAT phosphorylation and the specific recruitment of downstream signaling mediators to coreceptor-associated LAT molecules. These results point to a new function for CD4 and CD8 coreceptors in TCR signal transduction, namely to promote LAT phosphorylation by ZAP-70 by recruiting LAT to major histocompatibility complex–engaged TCR complexes.
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