Department of Infectious Diseases, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.
Department of Infectious Diseases, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.
Biochem Biophys Res Commun. 2020 May 21;526(1):199-205. doi: 10.1016/j.bbrc.2020.03.069. Epub 2020 Mar 19.
Upon detection of viral DNA, the cytoplasmic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) utilizes GTP and ATP as substrates to synthesize the second messenger molecule 2'3'cyclic GMP-AMP (cGAMP), which binds to the ER-associated adaptor protein MITA/STING to signal innate antiviral response to DNA virus. How the cGAS-MITA pathways are post-translationally regulated is not fully understood. In this study, we identified the tyrosine kinase CSK as a positive regulator of cGAS-MITA mediated innate antiviral response. CSK-deficiency inhibits DNA virus-triggered induction of downstream antiviral effector genes. Following DNA virus infection, CSK phosphorylates MITA at Y240 and Y245, which is important for its activation. These results suggest that CSK plays a role in modulating innate immune response to DNA virus.
当检测到病毒 DNA 时，细胞质 DNA 传感器环鸟苷酸-腺苷酸（cGAMP）合酶（cGAS）利用 GTP 和 ATP 作为底物合成第二信使分子 2'3'环鸟苷酸-腺苷酸（cGAMP），它与内质网相关衔接蛋白 MITA/STING 结合，以信号转导方式引发先天抗病毒反应来抵抗 DNA 病毒。cGAS-MITA 途径如何进行翻译后调控尚不完全清楚。在这项研究中，我们鉴定出酪氨酸激酶 CSK 是 cGAS-MITA 介导的先天抗病毒反应的正向调控因子。CSK 缺陷抑制 DNA 病毒触发的下游抗病毒效应基因的诱导。在 DNA 病毒感染后，CSK 在 Y240 和 Y245 处磷酸化 MITA，这对其激活很重要。这些结果表明，CSK 在调节先天免疫对 DNA 病毒的反应中发挥作用。
