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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, RyeojinPark, HanaLee, NawonSeo, JeonginJeong, WoojinLee, Soo Young
Ewha Authors
이수영정우진고려진
SCOPUS Author ID
이수영scopusscopus; 정우진scopus; 고려진scopus
Issue Date
2019
Journal Title
JOURNAL OF IMMUNOLOGY
ISSN
0022-1767JCR Link

1550-6606JCR Link
Citation
JOURNAL OF IMMUNOLOGY vol. 203, no. 11, pp. 2990 - 2999
Publisher
AMER ASSOC IMMUNOLOGISTS
Indexed
SCIE; SCOPUS WOS 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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