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 recept or (IL-1RI): human ''randomly sequenced cDNA 786'' (rsc786), murine My D88, and two partial Drosophila open reading frames, MstProx and STSDm 2245. Comparisons between these new proteins and known IL-1RI homologo us proteins such as Toll, 18-Wheeler, and T1/ST2 revealed six clusters of amino acid similarity. We tested the hypothesis that sequence simi larity between the signaling domain of IL-1RI and the three mammalian family members might indicate functional similarity. Chimeric IL-1RI r eceptors expressing the putative signaling domains of T1/ST2, MyD88, a nd rsc786 were assayed by three separate IL-1 responsive assays, NF-ka ppa B, phosphorylation of an epidermal growth factor receptor peptide, and an interleukin 8 promoter-controlled reporter construct, for thei r ability to transduce an IL-1-stimulated signal. All three assays wer e positive in response to the T1/ST2 chimera, while the MyD88 and rsc7 86 chimeras failed to respond. These data indicate that the sequence h omology between IL-1RI and T1/ST2 indicates a functional homology as w ell.