| First Author | Ko R | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 11 | Pages | 2990-2999 |
| PubMed ID | 31619538 | Mgi Jnum | J:282205 |
| Mgi Id | MGI:6379903 | Doi | 10.4049/jimmunol.1900685 |
| Citation | Ko R, et al. (2019) Glycogen Synthase Kinase 3beta Regulates Antiviral Responses of TLR3 via TRAF2-Src Axis. J Immunol 203(11):2990-2999 |
| abstractText | 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 GSK3beta regulates Src phosphorylation via TNFR-associated factor 2 (TRAF2)-mediated Src ubiquitination. GSK3beta 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 GSK3beta-TRAF2-Src axis. |
