Interleukin-1 receptor (IL1R)-associated kinases (IRAKs) are important mediators in the signal transduction of Toll-like receptor (TLR) and IL1R family members, collectively referred to as TIRs. Binding of IL-1 to its cognate receptor results in the activation of the NFkB signaling pathway. An IL-1-dependent kinase termed IRAK-1 (for IL-1 receptor- associated kinase 1) coimmunoprecipitates with activated IL-1RI and is implicated as an upstream mediator of NFkB activation. A related Drosophila protein, Pelle, is a known upstream activator of Dorsal, the Drosophila homolog of NFkB. IRAK-2 is a proximal mediator of IL1, a component of the IL1R signaling complex, and is required for IL1R-induced NFkB activation. IRAK-4, like IRAK-1 and Pelle, has auto- and cross-phosphorylation kinase activity. IRAK-4 is strongly expressed in kidney and is also found in lung, testis, small intestine, breast, liver, and placenta. In contrast to the other IRAKs that are expressed in most cell types, IRAK-M is restricted to monocytic cells. IRAK-M mRNA transcripts are found predominantly in PBL and the monocytic cell lines U937 and THP-1.