IRAK (Pelle) Family Member IRAK-2 and MyD88 as Proximal Mediators of IL-1 Signaling

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Science  28 Nov 1997:
Vol. 278, Issue 5343, pp. 1612-1615
DOI: 10.1126/science.278.5343.1612

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The interleukin-1 receptor (IL-1R) signaling pathway leads to nuclear factor kappa B (NF-κB) 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-1R–induced NF-κB activation: IRAK-2, a Pelle family member, and MyD88, a death domain–containing adapter molecule. Both associate with the IL-1R signaling complex. Dominant negative forms of either attenuate IL-1R–mediated NF-κB activation. Therefore, IRAK-2 and MyD88 may provide additional therapeutic targets for inhibiting IL-1–induced inflammation.

  • * Present address: Mario Negri Institute, Milano, Italy.

  • To whom correspondence should be addressed. Present address: Genentech, South San Francisco, CA 94080, USA. E-mail: dixit{at}

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