文章基本信息

标题：The tyrosine kinase c-Abl potentiates interferon-mediated antiviral immunity by STAT1 phosphorylation
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作者：Hainan Liu ; Yan Cui ; Yu Bai 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：2
页码：1-40
DOI：10.1016/j.isci.2021.102078
语种：English
出版社：Elsevier
摘要：SummaryInterferon (IFN)-induced activation of the signal transducer and activator of transcription (STAT) family is an important event in antiviral immunity. Here, we show that the nonreceptor kinases c-Abl and Arg directly interact with STAT1 and potentiate the phosphorylation of STAT1 on Y701. c-Abl/Arg could mediate STAT1 phosphorylation independent of Janus kinases in the absence of IFNγ and potentiate IFNγ-mediated STAT1 phosphorylation. Moreover, STAT1 dimerization, nuclear translocation, and downstream gene transcription are regulated by c-Abl/Arg. c-Abl/Arg (abl1/abl2) deficiency significantly suppresses antiviral responses in vesicular stomatitis virus-infected cells. Compared to vehicle, administration of the c-Abl/Arg selective inhibitor AMN107 resulted in significantly increased mortality in mice infected with human influenza virus. Our study demonstrates that c-Abl plays an essential role in the STAT1 activation signaling pathway and provides an important approach for antiviral immunity regulation.Graphical abstractDisplay OmittedHighlights•c-Abl/Arg mediates a JAK2-independent STAT1 phosphorylation•Abl kinase potentiates IFNγ-induced STAT1 phosphorylation and activation•c-Abl-mediated STAT1 phosphorylation contributes to IFN-induced antiviral effectsBiological Sciences; Virology; Viral Microbiology