CSK promotes innate immune response to DNA virus by phosphorylating MITA
CSK promotes innate immune response to DNA virus by phosphorylating MITA
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CSK 通过磷酸化 MITA 促进对 DNA 病毒的先天免疫反应
DOI：
10.1016/j.bbrc.2020.03.069
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发表时间：
2020-05-21
影响因子：
3.1
通讯作者：
Shu, Hong-Bing
中科院分区：
文献类型：
--
作者：
Gao, Peng;Hu, Ming-Ming;Shu, Hong-Bing
在检测到病毒DNA时，细胞质DNA传感器环GMP-AMP（cGAMP）合酶（cGAS）利用GTP和ATP作为底物来合成第二信使分子2'3 '环GMP-AMP（cGAMP），其结合ER相关衔接蛋白MITA/STING以发出对DNA病毒的先天性抗病毒应答的信号。cGAS-MITA途径如何在产后调节尚未完全了解。在这项研究中，我们确定了酪氨酸激酶CSK作为cGAS-MITA介导的先天性抗病毒反应的正调节因子。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，这对其活化是重要的。这些结果表明CSK在调节对DNA病毒的天然免疫应答中起作用。(C)2020爱思唯尔公司All rights reserved.
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. (C) 2020 Elsevier Inc. All rights reserved.