Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex

J Biol Chem. 2003 Mar 28;278(13):10952-6. doi: 10.1074/jbc.M212112200. Epub 2002 Dec 20.

Abstract

The signaling pathway downstream of the mammalian interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) is evolutionally conserved with that mediated by the Drosophila Toll protein. Toll initiates its signal through the adapter molecule Tube and the serine-threonine kinase Pelle. Pelle is highly homologous to members of the IL-1R-associated kinase (IRAK) family in mammals. Recently, a novel Pelle-interacting protein called Pellino was identified in Drosophila. We now report a mammalian counterpart of Pellino, termed Pellino 1, which is required for NF kappa B activation and IL-8 gene expression in response to IL-1, probably through its signal-dependent interaction with IRAK4, IRAK, and the tumor necrosis factor receptor-associated factor 6 (TRAF6). The Pellino 1-IRAK-IRAK4-TRAF6 signaling complex is likely to be intermediate, located between the IL-1 receptor complex and the TAK1 complex in the IL-1 pathway.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • DNA, Complementary
  • Gene Expression Regulation / physiology
  • Humans
  • Interleukin-1 / physiology*
  • Interleukin-1 Receptor-Associated Kinases
  • Interleukin-8 / genetics
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Precipitin Tests
  • Proteins / metabolism*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*
  • TNF Receptor-Associated Factor 6
  • Ubiquitin-Protein Ligases

Substances

  • DNA, Complementary
  • Interleukin-1
  • Interleukin-8
  • NF-kappa B
  • Nuclear Proteins
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • TNF Receptor-Associated Factor 6
  • PELI1 protein, human
  • Ubiquitin-Protein Ligases
  • Phosphotransferases (Alcohol Group Acceptor)
  • IRAK4 protein, human
  • Interleukin-1 Receptor-Associated Kinases