Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
J Immunol. 2012 Aug 15;189(4):1545-50. doi: 10.4049/jimmunol.1200405. Epub 2012 Jul 13.
Maf proteins are involved in a variety of biological processes, such as oncogenesis, lens development, and differentiation. In immune system, c-Maf transactivates IL-4 promoter, and ectopic expression of c-Maf skews primary T cell response toward the Th2 pathway. Numerous transcription factors are subjected to posttranslational modification. In this study, to our knowledge, we show for the first time that c-Maf is subjective to tyrosine phosphorylation in Th cells and that the level of its tyrosine phosphorylation positively correlates with IL-4 expression by peripheral Th cells, but is negatively associated with the severity of disease in NOD mice. c-Maf undergoes tyrosine phosphorylation at Tyr(21), Tyr(92), and Tyr(131) residues in Th2 cells. Furthermore, tyrosine phosphorylation at these three residues is critical for the recruitment of c-Maf to IL-4 promoter and IL-4 production in Th cells. Taken together, this study sheds new light on the role of posttranslational modification of c-Maf in IL-4 production and Th cell-mediated autoimmune diseases.
Maf 蛋白参与多种生物学过程，如肿瘤发生、晶状体发育和分化。在免疫系统中，c-Maf 反式激活 IL-4 启动子，c-Maf 的异位表达使原代 T 细胞反应偏向 Th2 途径。许多转录因子都受到翻译后修饰的影响。在这项研究中，据我们所知，我们首次表明 c-Maf 在 Th 细胞中受到酪氨酸磷酸化的影响，其酪氨酸磷酸化水平与外周 Th 细胞中 IL-4 的表达呈正相关，但与 NOD 小鼠疾病的严重程度呈负相关。c-Maf 在 Th2 细胞中的 Tyr(21)、Tyr(92)和 Tyr(131)残基上发生酪氨酸磷酸化。此外，这三个残基的酪氨酸磷酸化对于 c-Maf 募集到 IL-4 启动子和 Th 细胞中 IL-4 产生是至关重要的。总之，这项研究揭示了 c-Maf 翻译后修饰在 IL-4 产生和 Th 细胞介导的自身免疫性疾病中的作用。
