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Glycogen Synthase Kinase 3 beta Regulates Antiviral Responses of TLR3 via TRAF2-Src Axis
- Title
- Glycogen Synthase Kinase 3 beta Regulates Antiviral Responses of TLR3 via TRAF2-Src Axis
- Authors
- Ko, Ryeojin; Park, Hana; Lee, Nawon; Seo, Jeongin; Jeong, Woojin; Lee, Soo Young
- Ewha Authors
- 이수영; 정우진; 고려진
- SCOPUS Author ID
- 이수영; 정우진; 고려진
- Issue Date
- 2019
- Journal Title
- JOURNAL OF IMMUNOLOGY
- ISSN
- 0022-1767
1550-6606
- Citation
- JOURNAL OF IMMUNOLOGY vol. 203, no. 11, pp. 2990 - 2999
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- The protein tyrosine kinase Src regulates the synthesis of TLR3-mediated IFN-beta 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 GSK3 beta regulates Src phosphorylation via TNFR-associated factor 2 (TRAF2)-mediated Src ubiquitination. GSK3 beta deficiency in mouse embryonic fibroblasts significantly reduces polyinosinic:polycytidylic acid-induced IFN-beta 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 GSK3 beta-TRAF2-Src axis.
- DOI
- 10.4049/jimmunol.1900685
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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