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The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways.
- Source :
-
Cell reports [Cell Rep] 2022 Aug 16; Vol. 40 (7), pp. 111225. - Publication Year :
- 2022
-
Abstract
- Interleukin-1 receptor-associated kinases (IRAKs) -4, -2, and -1 are involved in transducing signals from Toll-like receptors (TLRs) via the adaptor myeloid differentiation primary-response protein 88 (MYD88). How MYD88/IRAK4/2/1 complexes are formed, their redundancies, and potential non-enzymatic roles are subjects of debate. Here, we examine the hierarchical requirements for IRAK proteins in the context of TLR4 activation and confirmed that the kinase activity of IRAK4 is essential for MYD88 signaling. Surprisingly, the IRAK4 scaffold is required for activation of the E3 ubiquitin ligase TNF receptor-associated factor 6 (TRAF6) by both MYD88 and TIR domain-containing adaptor protein inducing IFN-β (TRIF), a unique adaptation in the TLR4 response. IRAK4 scaffold is, therefore, essential in integrating MYD88 and TRIF in TLR4 signaling.<br />Competing Interests: Declaration of interests The authors declare no competing financial interests.<br /> (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Adaptor Proteins, Vesicular Transport metabolism
Humans
Signal Transduction physiology
Toll-Like Receptor 3 metabolism
Toll-Like Receptor 4 metabolism
Interleukin-1 Receptor-Associated Kinases metabolism
Myeloid Differentiation Factor 88 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 40
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 35977521
- Full Text :
- https://doi.org/10.1016/j.celrep.2022.111225