PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCθ
PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCθ
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DOI：
10.1016/j.febslet.2004.07.083
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发表时间：
2004-09-10
期刊：
影响因子：
3.5
通讯作者：
Chaudhary, D
中科院分区：
文献类型：
--
作者：
Sheppard, KA;Fitz, LJ;Chaudhary, D
免疫抑制受体-程序性死亡-1(PD-1)的参与减弱了T细胞受体(TCR)介导的IL-2产生的激活和T细胞的增殖。在这里，我们证明了PD-1对T细胞功能的调节包括抑制TCR介导的ZAP70的磷酸化以及与CD3zeta的关联。此外，PD-1信号减弱了同源TCR信号中PKCtheta激活环的磷酸化。PKCtheta已被证明是T细胞产生IL-2所必需的。与C端免疫受体酪氨酸开关基序(ITSM)相对应的磷酸化PD-1肽在体外可作为SHP-2和SHP-1的对接位点，而含有N端PD-1免疫受体酪氨酸抑制基序(ITIM)的磷酸化PD-1肽仅与SHP-2结合。(C)2004年，由Elsevier B.V.代表欧洲生化学会联合会出版。
Engagement of the immunoinhibitory receptor, programmed death-1 (PD-1) attenuates T-cell receptor (TCR)-mediated activation of IL-2 production and T-cell proliferation. Here, we demonstrate that PD-1 modulation of T-cell function involves inhibition of TCR-mediated phosphorylation of ZAP70 and association with CD3zeta. In addition, PD-1 signaling attenuates PKCtheta activation loop phosphorylation in a cognate TCR signal. PKCtheta has been shown to be required for T-cell IL-2 production. A phosphorylated PD-1 peptide, corresponding to the C-terminal immunoreceptor tyrosine-switch motif (ITSM), acts as a docking site in vitro for both SHP-2 and SHP-1, while the phosphorylated peptide containing the N-terminal PD-1 immunoreceptor tyrosine based inhibitory motif (ITIM) associates only with SHP-2. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.