A LAT mutation that inhibits T cell development yet induces lymphoproliferation
A LAT mutation that inhibits T cell development yet induces lymphoproliferation
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DOI：
10.1126/science.1069066
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发表时间：
2002-06-14
期刊：
影响因子：
56.9
通讯作者：
Love, PE
中科院分区：
文献类型：
--
作者：
Sommers, CL;Park, CS;Love, PE
LAT（T细胞活化接头）中单一酪氨酸突变纯合子小鼠表现出T细胞成熟的早期阻滞，但后来发展为多克隆淋巴增生性疾病和自身免疫性疾病的体征。T细胞抗原受体（TCR）诱导的磷脂酶C-γ 1（PLC-γ 1）和活化的T细胞的核因子的活化，钙内流，白细胞介素-2的产生，和细胞死亡的LAT突变小鼠的T细胞减少或废除。相反，TCR诱导的Erk活化是完整的。这些结果确定了通过LAT整合的PLC-γ 1和Ras-Erk信号在T细胞发育和稳态中的关键作用。
Mice homozygous for a single tyrosine mutation in LAT (linker for activation of T cells) exhibited an early block in T cell maturation but later developed a polyclonal lymphoproliferative disorder and signs of autoimmune disease. T cell antigen receptor (TCR)-induced activation of phospholipase C-gamma 1 (PLC-gamma1) and of nuclear factor of activated T cells, calcium influx, interleukin-2 production, and cell death were reduced or abrogated in T cells from LAT mutant mice. In contrast, TCR-induced Erk activation was intact. These results identify a critical role for integrated PLC-gamma1 and Ras-Erk signaling through LAT in T cell development and homeostasis.