T1/ST2 signaling establishes it as a member of an expanding interleukin-1 receptor family.
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.
Mitcham
J L
JL
Immunex Corporation, Seattle, Washington 98101, USA.
Parnet
P
P
Bonnert
T P
TP
Garka
K E
KE
Gerhart
M J
MJ
Slack
J L
JL
Gayle
M A
MA
Dower
S K
SK
Sims
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D016384:Consensus Sequence; D017931:DNA Primers; D004331:Drosophila melanogaster / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D007700:Kinetics; D008322:Mammals; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry* / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection
D017931:DNA Primers; C079241:IL1RL1 protein, human; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D016328:NF-kappa B; D011506:Proteins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D066246:ErbB Receptors