IRAK (Pelle) Family Member IRAK-2 and MyD88 as Proximal Mediators of IL-1 Signaling (Reprinted from Science, vol 278, pg 1612-1615, 1997)

The interleukin-1 receptor (IL-1R) signaling pathway leads to nuclear factor kappa B (NF-kappa B) activation in mammals and is similar to the Toll pathway in Drosophila: the IL-1R-associated kinase (IRAK) is homologous to Pelle. Two additional proximal mediators were identified that are required for IL-1-induced NF-kappa B activation: IRAK-2, a Pelle family member, and MyD88, a death domain-containing adapter molecule. Both associated with the IL-1R signaling complex. Dominant negative forms of either attenuate IL-1R-mediated NF-kappa B activation. Therefore, IRAK-2 and MyD88 may provide additional therapeutic targets for inhibiting IL-1-induced inflammation.