Abstract
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
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Line
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Chlorocebus aethiops
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Cloning, Molecular
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Consensus Sequence
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DNA Primers
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Drosophila melanogaster / metabolism
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ErbB Receptors / metabolism
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Humans
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Interleukin-1 Receptor-Like 1 Protein
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Kinetics
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Mammals
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Membrane Proteins*
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Mice
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Molecular Sequence Data
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NF-kappa B / metabolism
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Phosphorylation
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Protein Biosynthesis
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Proteins / chemistry*
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Proteins / physiology*
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Rats
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Receptors, Cell Surface
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Receptors, Interleukin
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Receptors, Interleukin-1 / biosynthesis
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Receptors, Interleukin-1 / chemistry*
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Receptors, Interleukin-1 / physiology*
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Signal Transduction*
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Transfection
Substances
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DNA Primers
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IL1RL1 protein, human
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Il1rl1 protein, mouse
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Interleukin-1 Receptor-Like 1 Protein
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Membrane Proteins
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NF-kappa B
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Proteins
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Receptors, Cell Surface
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Receptors, Interleukin
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Receptors, Interleukin-1
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Recombinant Fusion Proteins
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Recombinant Proteins
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ErbB Receptors