Overexpression of an enzymically inactive interleukin-1-receptor-associated kinase activates nuclear factor-κB

Upon interleukin 1 (IL-1) stimulation, the IL-1-receptor (IL-IR)associated kinase (IRAK) is rapidly recruited to the IL-IR complex and undergoes phosphorylation. Here we demonstrate that recombinant wild-type IRAK (IRAK-WT), but not a kinase-defective mutant with Asp(340) replaced by an asparagine residue (IRAK-Asp(390)Asn), is highly phosphorylated and is capable of auto-phosphorylation in vitro. Overexpression of both IRAK-WT and IRAK-sp(340)Asn caused activation of nuclear factor kappa B, suggesting that the kinase activity of IRAK is not required outside of the IL-IR complex.