Interleukin-1 receptor-associated kinase is a serine/threonine-specific kinase that can be coprecipitated in an IL-1-inducible manner with the IL-1 receptor. The mammalian family of IRAK molecules contains four members. The binding of IL-1 to IL-1 receptor type I initiates the formation of a complex that includes IL-1RI, AcP, MyD88, and IRAKs. IRAK undergoes autophosphorylation shortly after IL-1 stimulation. The subsequent events involve IRAK dissociation from the IL-1RI complex, its ubiquitination, and its association with two membrane-bound proteins: TAB2 and TRAF6. The resulting IRAK-TRAF6-TAB2 complex is then released into the cytoplasm where it activates protein kinase cascades, including TAK1, IKKs, and the stress-activated kinases.Upon IL-1R/TLR ligation, IRAK1 and IRAK4 are rapidly recruited to the receptor by the adaptor MyD88. IRAK1 is phosphorylated by IRAK4 at Thr209 and Thr387, followed by sequential autohyperphosphorylation in various domains.
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