IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase
TLDR
IRAK-4 is the closest human homolog to Pelle and depends on its kinase activity to activate NF-κB, suggesting a role of IRAK- 4 as a central element in the early signal transduction of Toll/IL-1 receptors, upstream of IRAk-1.Abstract:
Toll/IL-1 receptor family members are central components of host defense mechanisms in a variety of species. One well conserved element in their signal transduction is Ser/Thr kinases, which couple early signaling events in a receptor complex at the plasma membrane to larger signalosomes in the cytosol. The fruit fly Drosophila melanogaster has one member of this family of kinases, termed Pelle. The complexity of this pathway is vastly increased in vertebrates, and several Pelle homologs have been described and termed IL-1 receptor-associated kinase (IRAK). Here we report the identification of a novel and distinct member of the IRAK family, IRAK-4. IRAK-4 is the closest human homolog to Pelle. Endogenous IRAK-4 interacts with IRAK-1 and TRAF6 in an IL-1-dependent manner, and overexpression of IRAK-4 can activate NF-κB as well as mitogen-activated protein (MAP) kinase pathways. Most strikingly, and in contrast to the other IRAKs, IRAK-4 depends on its kinase activity to activate NF-κB. In addition, IRAK-4 is able to phosphorylate IRAK-1, and overexpression of dominant-negative IRAK-4 is blocking the IL-1-induced activation and modification of IRAK-1, suggesting a role of IRAK-4 as a central element in the early signal transduction of Toll/IL-1 receptors, upstream of IRAK-1.read more
Citations
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Cloning and functional characterization of IRAK4 in large yellow croaker (Larimichthys crocea) that associates with MyD88 but impairs NF-κB activation
Peng Fei Zou,Xue Na Huang,Cui Luan Yao,Qing Xue Sun,Ying Li,Qian Zhu,Zhen Xing Yu,Ze Jun Fan +7 more
TL;DR: Although Lc‐IRAK4 was evolutionarily conserved in vertebrates, the exact function especially the signaling transduction mediated by IRAK4 in fish immune response was different from that in mammals, which impaired MyD88‐mediated NF‐&kgr;B activation.
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Effects of Enterococcus faecalis lipoteichoic acid on receptor activator of nuclear factor-κB ligand and osteoprotegerin expression in periodontal ligament fibroblasts.
TL;DR: Enterococcus faecalis LTA could upregulate the expression of RankL and OPG at different rates, suggesting a potential role for LTA in the bone resorption process of refractory apical periodontitis through the regulation of RANKL andOPG.
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Dimeric Structure of the Pseudokinase IRAK3 Suggests an Allosteric Mechanism for Negative Regulation
TL;DR: The crystal structure of the human IRAK3 pseudokinase domain in a closed, pseudoactive conformation is reported and multiple conserved cysteine residues imply a potential redox control of IRAK2 conformation and dimerization.
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A novel interleukin-1 receptor-associated kinase-4 from thick shell mussel Mytilus coruscus is involved in inflammatory response.
TL;DR: Results collectively indicated that McIRAK4 is one member of IRAK4 subfamily and might play the potential signal transducer role in inflammatory response, and contributes to the clarification of the innate immune response in molluscs.
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