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

Research output: Contribution to journalArticlepeer-review

1 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 languageEnglish
Pages (from-to)2990-2999
Number of pages10
JournalJournal of Immunology
Volume203
Issue number11
DOIs
StatePublished - 1 Dec 2019

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