Frk positively regulates innate antiviral immunity by phosphorylating TBK1

被引：0

作者：

Zhang, Xiaomei ^{[1
]}

You, Ying ^{[2
]}

Xiong, Tingrong ^{[3
,4
]}

Zhang, Xiaokai ^{[3
]}

Wang, Haibo ^{[5
]}

Geng, Jinxia ^{[5
]}

Wang, Miao ^{[3
]}

Xu, Yanyan ^{[3
]}

Gao, Shanshan ^{[3
,4
]}

Wu, Xiaoyan ^{[3
]}

Zheng, Yue ^{[3
]}

Wen, Xianhua ^{[3
]}

Yang, Haoyu ^{[3
]}

Wang, Yu ^{[3
,5
]}

Wen, Xiaohua ^{[6
]}

Zhao, Congcong ^{[3
]}

机构：

[1] Third Mil Med Univ Army Med Univ, Xinqiao Hosp, Dept Med Engn, Chongqing, Peoples R China

[2] Third Mil Med Univ, Southwest Hosp, Clin Med Res Ctr, Chongqing, Peoples R China

[3] Third Mil Med Univ, Coll Pharm, Natl Engn Res Ctr Immunol Prod, Dept Microbiol & Biochem Pharm, Chongqing, Peoples R China

[4] Chongqing Univ, Sch Pharmaceut Sci, Chongqing Key Lab Nat Prod Synth & Drug Res, Chongqing, Peoples R China

[5] Third Mil Med Univ, Noncommissioned Officer Sch, Dept Basic Courses, Shijiazhuang, Peoples R China

[6] 980th Hosp Peoples Liberat Army Joint Logist Suppo, Dept Hlth Med, Shijiazhuang, Peoples R China

来源：

FRONTIERS IN MICROBIOLOGY | 2025年 / 16卷

基金：

中国国家自然科学基金;

关键词：

macrophages; Frk; TBK1; phosphorylation; IFN-I; HUMAN GLIOMA-CELLS; K63-LINKED UBIQUITINATION; KINASE; IDENTIFICATION; RECOGNITION; MIGRATION; PROLIFERATION; SUPPRESSES; INVASION; PATHWAY;

D O I：

10.3389/fmicb.2025.1525648

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Type I interferons (IFN-I) are crucial for the initial defense against viral infections. TBK1 serves as a key regulator in the production of IFN-I, with its phosphorylation being essential for the regulation of its activity. However, the regulatory mechanisms governing its activation remain incompletely elucidated. In this study, we validated the function of Fyn-related kinase (Frk) in the antiviral innate immune response and identified the direct target molecule of Frk in the IFN-beta signaling pathway. Furthermore, we elucidated the mechanism by which Frk phosphorylates TBK1 during infection and the role of Frk in IFN-beta production. We discovered that Frk enhances the activation of the IFN-I production pathway by targeting TBK1. Mechanistically, Frk promotes the K63 ubiquitination of TBK1 and subsequent activation of the transcription factor IRF3 by phosphorylating TBK1 at tyrosine residues 174 and 179, thereby enhancing the production of IFN-beta in macrophages. Employing both in vivo and in vitro viral infection assays, we demonstrated that IFN-beta mediated by Frk inhibits the replication of VSV or HSV-1 and alleviates lung lesions. Our findings indicate that Frk functions as a key regulator of TBK1 to strengthen antiviral immunity and represents a promising target for the development of antiviral drugs.

引用

页数：12

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