Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15105-10. doi: 10.1073/pnas.1005419107. Epub 2010 Aug 9.
The Fas receptor (also known as CD95 and APO-1) is a member of the tumor necrosis factor alpha-family of death receptors that mediate T-cell responses. Here, we show that Fas receptor signaling requires a functional T-cell receptor (TCR) complex. Fas receptor directly binds to and activates TCR components in a stimulus-dependent manner. Fas receptor stimulation does not activate canonical downstream TCR pathways, but instead the TCR complex is required specifically for Fas-mediated calcium release. Importantly, null mutations in Lck, ZAP70, and the TCR alpha- and beta-chains abrogate Fas signaling. Our results reveal a direct role for the TCR complex in mediating Fas-specific signaling events critical for T-cell homeostasis.
Fas 受体（也称为 CD95 和 APO-1）是肿瘤坏死因子-α家族死亡受体的成员，可介导 T 细胞反应。在这里，我们表明 Fas 受体信号需要功能性 T 细胞受体（TCR）复合物。Fas 受体以刺激依赖性的方式直接结合并激活 TCR 成分。Fas 受体刺激不会激活经典的下游 TCR 途径，而是 TCR 复合物是 Fas 介导的钙释放所必需的。重要的是，Lck、ZAP70 以及 TCR α 和 β 链的缺失突变会阻断 Fas 信号。我们的结果揭示了 TCR 复合物在介导 Fas 特异性信号事件中的直接作用，这些信号事件对 T 细胞稳态至关重要。
