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
相关论文
共 33 条
[21]   Structural Analysis of the STING Adaptor Protein Reveals a Hydrophobic Dimer Interface and Mode of Cyclic di-GMP Binding [J].
Ouyang, Songying ;
Song, Xianqiang ;
Wang, Yaya ;
Ru, Heng ;
Shaw, Neil ;
Jiang, Yan ;
Niu, Fengfeng ;
Zhu, Yanping ;
Qiu, Weicheng ;
Parvatiyar, Kislay ;
Li, Yang ;
Zhang, Rongguang ;
Cheng, Genhong ;
Liu, Zhi-Jie .
IMMUNITY, 2012, 36 (06) :1073-1086
[22]   Immune Sensing of DNA [J].
Paludan, Soren R. ;
Bowie, Andrew G. .
IMMUNITY, 2013, 38 (05) :870-880
[23]   Csk controls antigen receptor-mediated development and selection of T-lineage cells [J].
Schmedt, C ;
Saijo, K ;
Niidome, T ;
Kühn, R ;
Aizawa, S ;
Tarakhovsky, A .
NATURE, 1998, 394 (6696) :901-904
[24]   Functional development of Src tyrosine kinases during evolution from a unicellular ancestor to multicellular animals [J].
Segawa, Yuko ;
Suga, Hiroshi ;
Iwabe, Naoyuki ;
Oneyama, Chitose ;
Akagi, Tsuyoshi ;
Miyata, Takashi ;
Okada, Masato .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (32) :12021-12026
[25]   Adding to the STING [J].
Shu, Hong-Bing ;
Wang, Yan-Yi .
IMMUNITY, 2014, 41 (06) :871-873
[26]   Carboxyl-Terminal Src Kinase Binds CD28 upon Activation and Mutes Downstream Signaling [J].
Skanland, Sigrid S. ;
Tasken, Kjetil .
JOURNAL OF IMMUNOLOGY, 2019, 203 (04) :1055-1063
[27]   Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway [J].
Sun, Lijun ;
Wu, Jiaxi ;
Du, Fenghe ;
Chen, Xiang ;
Chen, Zhijian J. .
SCIENCE, 2013, 339 (6121) :786-791
[28]   ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization [J].
Sun, Wenxiang ;
Li, Yang ;
Chen, Lu ;
Chen, Huihui ;
You, Fuping ;
Zhou, Xiang ;
Zhou, Yi ;
Zhai, Zhonghe ;
Chen, Danying ;
Jiang, Zhengfan .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (21) :8653-8658
[29]   TRAF3 regulation of inhibitory signaling pathways in B and T lymphocytes by kinase and phosphatase localization [J].
Wallis, Alicia M. ;
Bishop, Gail A. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2018, 103 (06) :1089-1098
[30]   PTPN1/2-mediated dephosphorylation of MITA/STING promotes its 20S proteasomal degradation and attenuates innate antiviral response [J].
Xia, Tian ;
Yi, Xue-Mei ;
Wu, Xin ;
Shang, Jun ;
Shu, Hong-Bing .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (40) :20063-20069