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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-kappaB) 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-kappaB 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-kappaB activation. Therefore, IRAK-2 and MyD88 may provide additional therapeutic targets for inhibiting IL-1-induced inflammation.

Pubmed ID: 9374458


  • Muzio M
  • Ni J
  • Feng P
  • Dixit VM


Science (New York, N.Y.)

Publication Data

November 28, 1997

Associated Grants


Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Antigens, Differentiation
  • Carrier Proteins
  • Cell Line
  • Drosophila Proteins
  • Humans
  • Interleukin-1
  • Interleukin-1 Receptor-Associated Kinases
  • Molecular Sequence Data
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Proteins
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • TNF Receptor-Associated Factor 6
  • Transfection