1. Glycogen Synthase Kinase 3β Regulates Antiviral Responses of TLR3 via TRAF2-Src Axis.
- Author
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Ko R, Park H, Lee N, Seo J, Jeong W, and Lee SY
- Subjects
- Animals, Cells, Cultured, Glycogen Synthase Kinase 3 beta deficiency, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphorylation, RAW 264.7 Cells, Ubiquitination, Glycogen Synthase Kinase 3 beta metabolism, TNF Receptor-Associated Factor 2 metabolism, Toll-Like Receptor 3 metabolism, src-Family Kinases metabolism
- Abstract
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.)
- Published
- 2019
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