IRAK (PELLE) FAMILY MEMBER IRAK-2 AND MYD88 AS PROXIMAL MEDIATORS OF IL-1 SIGNALING

The interleukin-1 receptor (IL-1R) signaling pathway leads to nuclear factor kappa B (NF-kappa B) activation in mammals and is similar to th e Toll pathway in Drosophila: the IL-1R-associated kinase (IRAK) is ho mologous to Pelle. Two additional proximal mediators were identified t hat are required for IL-1R-induced NF-kappa B activation: IRAK-2, a Pe lle family member, and MyD88, a death domain-containing adapter molecu le. Both associate with the IL-IR signaling complex. Dominant negative forms of either attenuate IL-1R-mediated NF-kappa B activation. There fore, IRAK-2 and MyD88 may provide additional therapeutic targets for inhibiting IL-1-induced inflammation.