IRAK: A Kinase Associated with the Interleukin-1 Receptor

@article{Cao1996IRAKAK,
  title={IRAK: A Kinase Associated with the Interleukin-1 Receptor},
  author={Zhaodan Cao and William J. Henzel and Xiong-ying Gao},
  journal={Science},
  year={1996},
  volume={271},
  pages={1128 - 1131}
}
The pleiotropic biological activities of interleukin-1 (IL-1) are mediated by its type I receptor (IL-1RI). When the ligand binds, IL-1RI initiates a signaling cascade that results in the activation of the transcription regulator nuclear factor kappa B (NF-κB). A protein kinase designated IRAK (IL-1 receptor-associated kinase) was purified, and its complementary DNA was molecularly cloned. When human embryonic kidney cells (cell line 293) overexpressing IL-1RI or HeLa cells were exposed to IL-1… 
Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein.
  • J. Huang, X. Gao, S. Li, Z. Cao
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
TLDR
Overexpression of an IL-1RAcP mutant lacking its intracellular domain, the IRAK-binding domain, prevented the recruitment of IRAK to the receptor complex and blockedIL-1-induced NF-kappaB activation.
Cytosolic domain of the type I interleukin-1 receptor spontaneously recruits signaling molecules to activate a proinflammatory gene.
TLDR
Two previously unrecognized 63- and 83-kD kinases as well as a protein with an Mr similar to the recently cloned IL-1R-associated kinase, all of which associate spontaneously with the IL- 1Rcd are identified.
Phosphatidylinositol 3-Kinase in Interleukin 1 Signaling
TLDR
The results indicate that PI 3-kinase is a novel signal transducer in IL-1 signaling and that it may differentially mediate the activation of NFκB and AP-1.
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TLDR
The identification of a new TRAF family member is reported, designated TRAF6, which indicates that TRAF proteins may function as signal transducers for distinct receptor families and that TRAf6 participates in IL-1 signalling.
Interleukin-18 activates the IRAK-TRAF6 pathway in mouse EL-4 cells.
TLDR
It is concluded that IL-18/IL-18R-mediated signaling may share the IRAK/TRAF6 pathway through NF-kappa B activation with the IL-1/il-1 receptor system.
The Interleukin-1 Receptor-associated Kinase Is Degraded by Proteasomes following Its Phosphorylation*
TLDR
The nonspecific kinase inhibitor K-252b blocks IRAK phosphorylation and degradation, but does not inhibit IRAK association with theIL-1R1 indicating that translocation of IRAK to the IL-1 R1 and itsosphorylation are independent events.
The Interleukin-1 Receptor Accessory Protein (IL-1RAcP) Is Essential for IL-1-induced Activation of Interleukin-1 Receptor-associated Kinase (IRAK) and Stress-activated Protein Kinases (SAP Kinases)*
TLDR
IL-1RAcP is an indispensible molecule in the IL-1 receptor signal transduction complex, necessary to link events on the plasma membrane level to downstream signaling pathways, allowing IL- 1-dependent activation of transcription factors and gene expression.
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