IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling

Science. 1997 Nov 28;278(5343):1612-5. doi: 10.1126/science.278.5343.1612.

Abstract

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.

MeSH terms

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

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Carrier Proteins
  • Drosophila Proteins
  • Interleukin-1
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Proteins
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • TNF Receptor-Associated Factor 6
  • Protein Kinases
  • pll protein, Drosophila
  • Interleukin-1 Receptor-Associated Kinases
  • Protein Serine-Threonine Kinases

Associated data

  • GENBANK/AF026273