A model of IRAK1c regulation of inflammation

A model of IRAK1c regulation of inflammation. Upon TIR activation by the appropriate ligand, the Tollip-IRAK1 complex is recruited to the TIR receptor at the membrane and interacts with MyD88 and TRAF6. IRAK4 phosphorylates IRAK1 (1) resulting in IRAK1 autophosphorylation and activation (2). IRAK1 then disengages from the receptor complex of MyD88 and Tollip (3) but remains associated with TRAF6, resulting in activation of the NF-κB pathway and production of proinflammatory cytokines (4). The splice variant IRAK1c cannot be phosphorylated by IRAK4, does not undergo autophosphorylation, and thus does not activate downstream signaling events.

Publication

A Novel Splice Variant of Interleukin-1 Receptor (IL-1R)-Associated Kinase 1 Plays a Negative Regulatory Role in Toll/IL-1R-Induced Inflammatory Signaling . (2005) Navin Rao, et al. Mol Cell Biol. 2005 Aug;25(15):6521-6532. Figure: F8. All organisms Mus musculus Homo sapiens Danio rerio

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