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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The Interleukin 1 (IL-1) Receptor Accessory Protein Toll/IL-1 Receptor Domain ANALYSIS OF PUTATIVE INTERACTION SITES BY IN VITRO MUTAGENESIS AND MOLECULAR MODELING
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TL;DR: The final structure of the IL-1 receptor accessory protein TIR domain suggests the conserved regions box 1 and 2, including Pro-446, as well as box 3 within the C-terminal α-helix as possible protein-protein interaction sites due to their exposure and their electrostatic potential.
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TL;DR: In this article, the effect of apoE on intracellular signaling by interleukin-1β (IL-1α), a proinflammatory cytokine present in atherosclerotic lesions, was investigated.
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Lancemaside A inhibits lipopolysaccharide-induced inflammation by targeting LPS/TLR4 complex.
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The Role of Toll-Like Receptor Signaling in Human Immunodeficiencies
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TL;DR: A review of recently described deficiencies reported in patients with various infectious diseases, highlighting the published data associating TLR polymorphism with an altered susceptibility to infectious diseases.
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Expression of alternatively spliced interleukin-1 receptor accessory protein mRNAs is differentially regulated during inflammation and apoptosis
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