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CD3 胞浆区Tyr突变阻断下游的细胞凋亡信号传递 |
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何亦平 刘彦信 肖声 刘士廉 郑德先
摘 要 目的：利用稳定表达CD8ε融合分子的细胞凋亡模型，研究其CD3ε-ITAM中两个酪氨酸的突变对细胞凋亡信号传递及相关基因表达的影响。方法：将稳定表达CD8ε融合分子及其3种突变分子的T淋巴细胞分别用抗CD8单抗刺激后，检测4种细胞蛋白酪氨酸磷酸化和胞浆Ca2+浓度的变化以及细胞凋亡相关基因表达。结果：抗体刺激后，表达CD8ε的细胞与表达其3种突变分子的细胞相比，其蛋白磷酸化增加，胞浆Ca2+浓度升高；立早基因nur77和细胞凋亡基因fas表达水平升高。结论：首次发现CD3ε-ITAM中两个酪氨酸的突变阻断了CD3介导的凋亡信号传导途径，并影响nur77和fas基因的表达。
关键词 细胞凋亡信号 酪氨酸突变 CD3ε分子
中国图书分类号 R392.12
Mutation of tyrosines in the cytoplasmic domain of CD3ε
blocks the apoptotic signaling pathway of T lymphocytes
HE Yi-Ping,LIU Yan-Xin,XIAO Sheng et al.
National Laboratories of Medical Molecular Biology,Chinese Academy of Medical Sciences & Peking Union Medical College， Beijing 100005
Abstract Objective：To study the effect of the mutation of two tyrosines in CD3ε-ITAM on apoptotic signaling pathway by using the cell lines stably expressed CD8ε chimera molecule and its mutants of tyrosines to phenolanalines in CD3ε-ITAM as models.Methods：The cells were stimulated with anti-CD8 monoclonal antibody and the protein phosphorylation was analyzed by Western-blot,concentration of Ca2+ analyzed by flow cytometry and nur77 and fas gene expressions determined by Northern-blot and RT-PCR respectively.Results:It was showed that the protein phosphorylations and intracellular concentrations of Ca2+ were increased,nur77 and fas gene expressions upregulated in the cells with expression of CD8ε+,but not in the cells with the expression of CD8ε mutants.Conclusion:It was found at the first time that mutation of any one of the two tyrosines in CD3ε-ITAM blocks the apoptotic signaling pathway mediated by CD3ε molecule.
Key words Cell apoptotic signaling Mutation of tyrosines CD3ε molecule
T淋巴细胞抗原受体(TCR)与CD3分子各亚单位(CD3γ、δ、ε和ζ)形成稳定的复合物，传递外界抗原刺激信号，引起细胞的激活或凋亡。T细胞激活和凋亡信号的传递主要是通过[1] [2] [3] 下一页
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