CSK promotes innate immune response to DNA virus by phosphorylating MITA

被引:14
作者
Gao, Peng [1 ]
Hu, Ming-Ming [1 ]
Shu, Hong-Bing [1 ]
机构
[1] Wuhan Univ, Zhongnan Hosp, Med Res Inst, Dept Infect Dis, Wuhan 430071, Peoples R China
基金
中国国家自然科学基金;
关键词
DNA virus; MITA; CSK; Tyrosine phosphorylation; Innate immune response; TYROSINE KINASES; RECOGNITION; SENSOR; COMPLEX; GENE; CGAS;
D O I
10.1016/j.bbrc.2020.03.069
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:199 / 205
页数:7
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