Glycogen synthase kinase 3b regulates antiviral responses of TLR3 via TRAF2-Src Axis

Ryeojin Ko; Hana Park; Nawon Lee; Jeongin Seo; Woojin Jeong; Soo Young Lee

doi:10.4049/jimmunol.1900685

Glycogen synthase kinase 3b regulates antiviral responses of TLR3 via TRAF2-Src Axis

Ryeojin Ko, Hana Park, Nawon Lee, Jeongin Seo, Woojin Jeong, Soo Young Lee

Department of Life Science

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

The protein tyrosine kinase Src regulates the synthesis of TLR3-mediated IFN-b via the TBK1-IFN regulatory factor 3 axis. However, the molecular mechanisms regulating Src activity in TLR3 signaling remain unclear. In this study, we report that GSK3b regulates Src phosphorylation via TNFR-associated factor 2 (TRAF2)-mediated Src ubiquitination. GSK3b deficiency in mouse embryonic fibroblasts significantly reduces polyinosinic:polycytidylic acid-induced IFN-b and IFN-stimulated gene expression, which is caused by diminished phosphorylation of Src at tyrosine 416. Src undergoes polyinosinic:polycytidylic acid- dependent lysine 63 chain ubiquitination, and TRAF2 is a direct E3 ligase for Src. Our study reveals novel mechanisms underlying TLR3-mediated antiviral responses mediated via the GSK3b-TRAF2-Src axis.

Original language	English
Pages (from-to)	2990-2999
Number of pages	10
Journal	Journal of Immunology
Volume	203
Issue number	11
DOIs	https://doi.org/10.4049/jimmunol.1900685
State	Published - 1 Dec 2019

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© 2019 by The American Association of Immunologists, Inc.

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title = "Glycogen synthase kinase 3b regulates antiviral responses of TLR3 via TRAF2-Src Axis",

abstract = "The protein tyrosine kinase Src regulates the synthesis of TLR3-mediated IFN-b via the TBK1-IFN regulatory factor 3 axis. However, the molecular mechanisms regulating Src activity in TLR3 signaling remain unclear. In this study, we report that GSK3b regulates Src phosphorylation via TNFR-associated factor 2 (TRAF2)-mediated Src ubiquitination. GSK3b deficiency in mouse embryonic fibroblasts significantly reduces polyinosinic:polycytidylic acid-induced IFN-b and IFN-stimulated gene expression, which is caused by diminished phosphorylation of Src at tyrosine 416. Src undergoes polyinosinic:polycytidylic acid- dependent lysine 63 chain ubiquitination, and TRAF2 is a direct E3 ligase for Src. Our study reveals novel mechanisms underlying TLR3-mediated antiviral responses mediated via the GSK3b-TRAF2-Src axis.",

author = "Ryeojin Ko and Hana Park and Nawon Lee and Jeongin Seo and Woojin Jeong and Lee, {Soo Young}",

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AU - Seo, Jeongin

AU - Jeong, Woojin

AU - Lee, Soo Young

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AB - The protein tyrosine kinase Src regulates the synthesis of TLR3-mediated IFN-b via the TBK1-IFN regulatory factor 3 axis. However, the molecular mechanisms regulating Src activity in TLR3 signaling remain unclear. In this study, we report that GSK3b regulates Src phosphorylation via TNFR-associated factor 2 (TRAF2)-mediated Src ubiquitination. GSK3b deficiency in mouse embryonic fibroblasts significantly reduces polyinosinic:polycytidylic acid-induced IFN-b and IFN-stimulated gene expression, which is caused by diminished phosphorylation of Src at tyrosine 416. Src undergoes polyinosinic:polycytidylic acid- dependent lysine 63 chain ubiquitination, and TRAF2 is a direct E3 ligase for Src. Our study reveals novel mechanisms underlying TLR3-mediated antiviral responses mediated via the GSK3b-TRAF2-Src axis.

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Glycogen synthase kinase 3b regulates antiviral responses of TLR3 via TRAF2-Src Axis

Abstract

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