Phosphatidylinositide 3-kinase priming couples c-FLIP to T cell activation
Phosphatidylinositide 3-kinase priming couples c-FLIP to T cell activation
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DOI：
10.1074/jbc.m303860200
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发表时间：
2004-01-02
影响因子：
4.8
通讯作者：
Lai, MZ
中科院分区：
文献类型：
--
作者：
Fang, LW;Tai, TS;Lai, MZ
细胞FLICE（FADD样白细胞介素-1-β转化酶）抑制蛋白（c-FLIP）通过与FADD（Fas相关死亡结构域蛋白）和caspase-8前体结合抑制死亡受体诱导的细胞凋亡。cFLIP还显示出传递激活信号并增强白细胞介素（IL）-2的产生。然而，c-FLIP介导的T细胞活化在大多数细胞中难以检测。我们发现，在DO11.10 T细胞中，c-FLIP表达导致IL-2产生的抑制，与Jurkat细胞中容易检测到的c-FLIP诱导的激活相反。直接比较显示，不同的信号通路的调节c-FLIP在Jurkat细胞和DO11.10细胞。我们研究了组成性激活的磷脂酰肌醇3-激酶（PI 3 K）是否在Jurkat细胞刺激c-FLIP。抑制Jurkat细胞中的PI 3 K消除了c-FLIP介导的IL-2产生的增加。此外，c-FLIP与活性PI 3 K协同激活ERK。此外，将PTEN引入Jurkat细胞消除了c-FLIP对IL-2产生和ERK激活的刺激作用。我们的研究结果表明，用PI 3 K引发促进c-FLIP与T细胞活化的偶联。
Cellular FLICE (FADD-like interleukin-1-beta-converting enzyme)-inhibitory protein (c-FLIP) inhibits death receptor-induced apoptosis by binding to FADD ( Fas-associated death domain protein) and pro-caspase-8. cFLIP has also been shown to transmit activation signals and to enhance interleukin (IL)-2 production. However, c-FLIP-mediated T cell activation is difficult to detect in most cells. We found that in DO11.10 T cells, c-FLIP expression led to inhibition of IL-2 production, in contrast to the readily detectable c-FLIP-induced activation in Jurkat cells. A direct comparison revealed that distinct signal pathways were regulated by c-FLIP in Jurkat cells and DO11.10 cells. We investigated whether constitutively activated phosphatidylinositide 3-kinase (PI3K) in Jurkat cells stimulated c-FLIP. Inhibition of PI3K in Jurkat cells abrogated a c-FLIP-mediated increase in IL-2 production. In addition, c-FLIP coordinated with active PI3K for ERK activation. Furthermore, introduction of PTEN back into Jurkat cells eliminated the stimulatory effect of c-FLIP on IL-2 production and ERK activation. Our results suggest that priming with PI3K promotes the coupling of c-FLIP to T cell activation.