IRAK-M Antibody #4369

Interleukin-1 (IL-1) receptor-associated kinase (IRAK) is a serine/threonine-specific kinase that can be coprecipitated in an IL-1-inducible manner with the IL-1 receptor (1). The mammalian family of IRAK molecules contains four members (IRAK1, IRAK2, IRAK3/IRAK-M, and IRAK4). The binding of IL-1 to IL-1 receptor type I (IL-1RI) initiates the formation of a complex that includes IL-1RI, AcP, MyD88, and IRAKs (2). 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 (3).
Unlike IRAK1 and IRAK4, IRAK2 and IRAK-M do not have significant kinase activity although they can still activate NF-κB when overexpressed (4). Expression of IRAK-M is more restricted compared to other family members with highest levels of expression occurring in monocytes/macrophages (4). Studies from IRAK-M knockout mice suggest that IRAK-M may play a role as a negative regulator of Toll-like receptor signaling and innate immune responses by preventing the dissociation of IRAK1 and IRAK4 from MyD88 and the subsequent formation of its complex with TRAF6 (5).