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Science 28 November 1997:
Vol. 278. no. 5343, pp. 1612 - 1615
DOI: 10.1126/science.278.5343.1612
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Reports

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

Marta Muzio, * Jian Ni, Ping Feng, Vishva M. Dixit dagger

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-1R-induced NF-kappa B 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-kappa B activation. Therefore, IRAK-2 and MyD88 may provide additional therapeutic targets for inhibiting IL-1-induced inflammation.

M. Muzio and V. M. Dixit, University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109, USA.
J. Ni and P. Feng, Human Genome Sciences, Rockville, MD 20850-9998, USA.
*   Present address: Mario Negri Institute, Milano, Italy.

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

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Science. ISSN 0036-8075 (print), 1095-9203 (online)