T1/ST2 signaling establishes it as a member of an expanding interleukin-1 receptor family

J Biol Chem. 1996 Mar 8;271(10):5777-83. doi: 10.1074/jbc.271.10.5777.


Through data base searches, we have discovered new proteins that share homology with the signaling domain of the type I interleukin-1 receptor (IL-1RI): human "randomly sequenced cDNA 786" (rsc786), murine MyD88, and two partial Drosophila open reading frames, MstProx and STSDm2245. Comparisons between these new proteins and known IL-1RI homologous proteins such as Toll, 18-Wheeler, and T1/ST2 revealed six clusters of amino acid similarity. We tested the hypothesis that sequence similarity between the signaling domain of IL-1RI and the three mammalian family members might indicate functional similarity. Chimeric IL-1RI receptors expressing the putative signaling domains of T1/ST2, MyD88, and rsc786 were assayed by three separate IL-1 responsive assays, NF-kappaB, phosphorylation of an epidermal growth factor receptor peptide, and an interleukin 8 promoter-controlled reporter construct, for their ability to transduce an IL-1-stimulated signal. All three assays were positive in response to the T1/ST2 chimera, while the MyD88 and rsc786 chimeras failed to respond. These data indicate that the sequence homology between IL-1RI and T1/ST2 indicates a functional homology as well.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Consensus Sequence
  • DNA Primers
  • Drosophila melanogaster / metabolism
  • ErbB Receptors / metabolism
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Kinetics
  • Mammals
  • Membrane Proteins*
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Phosphorylation
  • Protein Biosynthesis
  • Proteins / chemistry*
  • Proteins / physiology*
  • Rats
  • Receptors, Cell Surface
  • Receptors, Interleukin
  • Receptors, Interleukin-1 / biosynthesis
  • Receptors, Interleukin-1 / chemistry*
  • Receptors, Interleukin-1 / physiology*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Transfection


  • DNA Primers
  • IL1RL1 protein, human
  • Il1rl1 protein, mouse
  • Interleukin-1 Receptor-Like 1 Protein
  • Membrane Proteins
  • NF-kappa B
  • Proteins
  • Receptors, Cell Surface
  • Receptors, Interleukin
  • Receptors, Interleukin-1
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • ErbB Receptors

Associated data

  • GENBANK/U42425