Priming Phosphorylation of TANK-Binding Kinase 1 by IκB Kinase β Is Essential in Toll-Like Receptor 3/4 Signaling.
In: Molecular & Cellular Biology, Jg. 40 (2020-03-01), Heft 5, S. 1-14
academicJournal
Zugriff:
TRIF is an essential adaptor for Toll-like receptor 3/4 (TLR3/4) signaling to activate transcription factor interferon regulatory factor 3 (IRF-3). We examined the molecular mechanism of TLR3 signaling and found that TLR3 stimulation by double-stranded RNA (dsRNA) induces phosphorylation of TRIF at Ser210 and is required for IRF-3 recruitment. TANK-binding kinase 1 (TBK1) is known to be responsible for IRF-3 phosphorylation and activation. We found that TBK1 is also responsible for phosphorylation of Ser210 in TRIF. Unexpectedly, we discovered that IB kinase (IKKβ) plays an essential role in TLR3/4 signaling using a pharmacological inhibitor and gene deletion. Of note, IKKβ is essential in TLR3/4 but not in retinoic acidinducible gene I (RIG-I) signaling. Mechanistically, IKKβ transiently associates with and induces the phosphorylation of TBK1 upon TLR3 stimulation. These results suggest a phosphorylation cascade of IKKβ and TBK1, where priming phosphorylation of TBK1 by IKKβ is required to surpass the threshold to induce signaling, thereby activating IRF-3. [ABSTRACT FROM AUTHOR]
Titel: |
Priming Phosphorylation of TANK-Binding Kinase 1 by IκB Kinase β Is Essential in Toll-Like Receptor 3/4 Signaling.
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Autor/in / Beteiligte Person: | Abe, Hiroto ; Satoh, Junko ; Shirasaka, Yutaro ; Kogure, Amane ; Kato, Hiroki ; Ito, Shinji ; Fujita, Takashi |
Zeitschrift: | Molecular & Cellular Biology, Jg. 40 (2020-03-01), Heft 5, S. 1-14 |
Veröffentlichung: | 2020 |
Medientyp: | academicJournal |
ISSN: | 0270-7306 (print) |
DOI: | 10.1128/MCB.00509-19 |
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