ArticleThe Journal of experimental medicine2007
Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor-mediated immune responses but not in TCR signaling.
Article in The Journal of experimental medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 179 citations in OpenAlex.
- Randomized Placebo-Controlled, Biomarker-Stratified Phase Ib Microbiome Modulation in Melanoma: Impact of Antibiotic Preconditioning on Microbiome and Immunity.Cancer discovery · 2024Trial
- The Interleukin-1 Receptor-Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial.Arthritis & rheumatology (Hoboken, N.J.) · 2021Trial
- IRAK4 autophosphorylation functions as a molecular switch to regulate death domain assembly and Myddosome maturation.Nature communications · 2026Article
- A heterobifunctional IRAK4-targeting degrader impairs myddosome signaling in acute kidney injury and ameliorates kidney fibrosis.Communications biology · 2026Article
- Phosphoregulation of interleukin-1 receptor-associated kinase 1 in inflammatory signaling.Frontiers in immunology · 2026Review
- Enhancing Cancer Therapy with TLR7/8 Agonists: Applications in Vaccines and Combination Treatments.Cancers · 2025Review
- Short-term heavy drinking in a non-human primate model skews monocytes toward a hypo-inflammatory phenotype.Frontiers in immunology · 2025Article
- Degradation of IRAK4 for the treatment of lipopolysaccharide-induced acute lung injury in mice.Frontiers in pharmacology · 2025Article
- Emerging interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors or degraders as therapeutic agents for autoimmune diseases and cancer.Acta pharmaceutica Sinica. B · 2024Review
- IRAK4 is an immunological checkpoint in neuropsychiatric systemic lupus erythematosus.Scientific reports · 2024Article
- A Tiny Pocket Packs a Punch: Leveraging Pyridones for the Discovery of CNS-Penetrant Aza-indazole IRAK4 Inhibitors.ACS medicinal chemistry letters · 2024Article
- The IRAK1/IRF5 axis initiates IL-12 response by dendritic cells and control of Toxoplasma gondii infection.Cell reports · 2024Article
- Unraveling Extremely DamagingJournal of personalized medicine · 2023Article
- Emerging trends in IRAK-4 kinase research.Molecular biology reports · 2023Review
- Identification of a heterozygous pathogenic variant in IRAK4 in an adult patient with pneumococcal sepsis, monoclonal gammopathy of uncertain significance, and idiopathic systemic capillary leak syndrome.The journal of allergy and clinical immunology. Global · 2023Article
- Shedding light on the molecular and regulatory mechanisms of TLR4 signaling in endothelial cells under physiological and inflamed conditions.Frontiers in immunology · 2023Review
- Regulation of innate immune signaling by IRAK proteins.Frontiers in immunology · 2023Review
- Inhibition of IRAK 1/4 alleviates colitis by inhibiting TLR4/ NF-κB pathway and protecting the intestinal barrier.Bosnian journal of basic medical sciences · 2022Article
- The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways.Cell reports · 2022Article
- IRAK4 Signaling Drives Resistance to Checkpoint Immunotherapy in Pancreatic Ductal Adenocarcinoma.Gastroenterology · 2022Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Interleukin-1 receptor-associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)- and T cell receptor (TCR)-mediated signaling leading to the activation of nuclear factor kappaB (NF-kappaB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4(KN/KN) mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4(KN/KN) as well as IRAK-4(-/-) macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1-dependent and -independent pathways were involved in early induction of NF-kappaB-regulated genes in response to TLR ligands such as tumor necrosis factor alpha and IkappaBzeta. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927-1932), the TCR signaling was not impaired in IRAK-4(-/-) and IRAK-4(KN/KN) mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.
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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.