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The tyrosine kinase c-Abl potentiates interferon-mediated antiviral immunity by STAT1 phosphorylation.


ABSTRACT: Interferon (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 IFN? and potentiate IFN?-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.

SUBMITTER: Liu H 

PROVIDER: S-EPMC7887405 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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The tyrosine kinase c-Abl potentiates interferon-mediated antiviral immunity by STAT1 phosphorylation.

Liu Hainan H   Cui Yan Y   Bai Yu Y   Fang Yi Y   Gao Ting T   Wang Guangfei G   Zhu Lin L   Dong Qincai Q   Zhang Shuwei S   Yao Yi Y   Song Caiwei C   Niu Xiayang X   Jin Yanwen Y   Li Ping P   Cao Cheng C   Liu Xuan X  

iScience 20210121 2


Interferon (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 dow  ...[more]

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