ArticleCell reports2022
The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- Deficiency of protein kinase Cδ reprograms macrophage immunometabolism to suppress pyroptosis and stabilize atherosclerotic plaques.Experimental & molecular medicine · 2026Article
- Amelioration of Listeria monocytogenes infection in mice by live and pasteurized Faecalibacterium prausnitzii and its cell-free supernatant and its association with strengthened gut barrier and downregulated TLR4/NF-κB pathway.Probiotics and antimicrobial proteins · 2026Article
- Machine Learning-Driven Drug Repositioning Identifies Putative IRAK4 Inhibitors Through Structure-Based Computational Evaluation.Current issues in molecular biology · 2026Article
- Exercise-Induced Skeletal Muscle Secretory Factors and Macrophage Functional Remodeling: Mechanistic Advances.International journal of molecular sciences · 2026Review
- Oxidized Low-Density Lipoprotein Enhances Toll-like Receptor-Mediated Osteoclastogenic Responses in the Absence of Exogenous RANKL: Implications for Inflammatory Osteoclastogenesis in Periodontitis.Medicina (Kaunas, Lithuania) · 2026Article
- Review
- Structural basis for selective and potent degradation of IRAK4 by KT-474.Nature communications · 2026Article
- A heterobifunctional IRAK4-targeting degrader impairs myddosome signaling in acute kidney injury and ameliorates kidney fibrosis.Communications biology · 2026Article
- Radiolysis Derivatives fromMolecules (Basel, Switzerland) · 2026Article
- TLR4 Inhibition Attenuates Vascular Remodeling in A Mouse Model of Chronic Kidney Disease.Journal of atherosclerosis and thrombosis · 2026Article
- Integration of Transcriptomics and Mammary Epithelial Cell Models Reveals the Regulatory Mechanism of CXCR1 in E. Coli-Induced Bovine Mastitis.Applied biochemistry and biotechnology · 2026Article
- Neuroimmune cross-talk inFrontiers in immunology · 2026Review
- Immune signaling as a determinant of cellular identity and tissue function.Frontiers in immunology · 2026Review
- TLR25 is endosomally located and responds toFrontiers in immunology · 2026Article
- Modulation of macrophage survival duringFrontiers in cellular and infection microbiology · 2026Review
- RNA stability: a novel perspective on gene regulatory networks in bovine mastitis.BMC genomics · 2025Article
- Targeting Microglial Activation to Modulate Neuroinflammation in Alzheimer's Disease.Neuromolecular medicine · 2025Review
- Pseudomonas aeruginosa-derived DnaJ functions as a novel immunomodulator inducing IFNβ via CME-SGK1-IRF3 axis in macrophages.Scientific reports · 2025Article
- [Hypaphorine alleviates Crohn's disease-like colitis in mice by inhibiting intestinal epithelial inflammatory response and protecting intestinal barrier function].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.