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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Patent
Irak degraders and uses thereof
TL;DR: In this paper, the authors present compounds, compositions thereof, and methods of using the same, including an IRAK binding moiety capable of binding to IRAK4 and a degradation inducing moiety (DIM).
Book ChapterDOI
Ubiquitin Signaling to NF-κB
Natalie A. Borg,Vishva M. Dixit +1 more
TL;DR: An overview of some of the best-characterized NF-κB signaling pathways, highlighting their regulation by ubiquitin-mediated events and emphasizing the role of ubiqu itin ligases, deubiquitinases, and ubiquit in-binding molecules in regulating this crucial family of transcription factors.
Journal ArticleDOI
Ontogeny and expression analysis of tube (interleukin-1 receptor-associated kinase-4 homolog) from Penaeus monodon in response to white spot syndrome virus infection and on exposure to ligands
TL;DR: The ubiquitous expression of Pm IRAK-4 in different larval and post-larval stages implies the involvement of the gene in defense mechanism during early developmental stages of P. monodon and its possible role in immune responses in shrimp.
Book ChapterDOI
Other TLR Pathway Defects
TL;DR: IRAK-4- and MyD88-deficient patients suffer from recurrent pyogenic bacterial infections, particularly invasive infections by Streptococcus pneumoniae and, to a lesser extent, Staphylococcus aureus and Pseudomonas aeruginosa, and remain normally resistant to other microorganisms.
References
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Journal ArticleDOI
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Journal ArticleDOI
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