T1/ST2 Signaling Establishes It as a Member of an Expanding Interleukin-1 Receptor Family

doi:10.1074/jbc.271.10.5777

T1/ST2 Signaling Establishes It as a Member of an Expanding Interleukin-1 Receptor Family (*)

From the From Immunex Corporation, Seattle, Washington 98101

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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-κB, 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.

Footnotes

↵^§ Supported by a NATO fellowship. Permanent address: U394 INSERM, Rue Camille St.-Saens, Domaine de Carreire, 33077 Bordeaux Cedex, France.
↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(™)/EMBL Data Bank with accession number(s) U42425.
↵¹ The abbreviations used are:

IL-1

interleukin 1

IL-1RI

type I interleukin 1 receptor

rsc786

randomly sequenced cDNA 786

IL-1R AcP

interleukin 1 receptor accessory protein

ORF

open reading frame

EGFR

epidermal growth factor receptor.
↵²T. Bonnert, manuscript in preparation.
↵³J. Mitcham, unpublished results.
↵⁴T. Taguchi, J. Mitcham, S. Dower, J. Sims, and J. Testa, submitted for publication.
- Received August 30, 1995.
- Revision received October 24, 1995.