Glycogen Synthase Kinase 3β Regulates Antiviral Responses of TLR3 via TRAF2-Src Axis
- 등재 SCOPUS
- 발행기관 NLM (Medline)
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000162483
- 본문언어 영어
- Published As http://dx.doi.org/10.4049/jimmunol.1900685
초록/요약
The protein tyrosine kinase Src regulates the synthesis of TLR3-mediated IFN-β 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 GSK3β regulates Src phosphorylation via TNFR-associated factor 2 (TRAF2)-mediated Src ubiquitination. GSK3β deficiency in mouse embryonic fibroblasts significantly reduces polyinosinic:polycytidylic acid-induced IFN-β 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 GSK3β-TRAF2-Src axis. Copyright © 2019 by The American Association of Immunologists, Inc.
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