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Papers In Press, published online ahead of print July 5, 2000
Department of Molecular Biology, Immunex Corporation, Seattle, WA 98101
Corresponding Author: simsj{at}immunex.com
Two novel members of the interleukin-1 receptor (IL-1R) family, identified by homology searches of human genomic sequence databases, are described. The genes have been named according to their structural features: three immunoglobulin domain-containing IL-1 receptor related (TIGIRR)-1 and TIGIRR-2. TIGIRR-2 has recently been identified as causing mental retardation when mutated (1) and called IL1RAPL, a name we will also use henceforth. Neither receptor alone was able to mediate transcriptional activation of NF
J. Biol. Chem, 10.1074/jbc.M004077200
Submitted on May 12, 2000
Revised on July 5, 2000
Accepted on July 5, 2000
Identification and characterization of two members of a novel class of the IL-1R family: delineation of a new class of IL-1R-related proteins based on signaling
B in response to IL-1
, IL-1
or IL-18. In order to begin to elucidate the function of these and other orphan IL-1R family members, we have developed a functional assay utilizing a panel of chimeric receptors containing the extracellular and transmembrane domains of either type I IL-1R or IL-1R Accessory Protein (AcP) coupled to the cytoplasmic domains of all family members. Coexpression of each IL-1R-chimera with each AcP-chimera and an NFB-responsive reporter demonstrated that the cytoplasmic domains could be classified as IL-1R-like, AcP-like or neither. Any IL-1R-like cytoplasmic domain could cooperate with any AcP-like cytoplasmic domain. The TIGIRR-1 and IL1RAPL cytoplasmic domains, however, were unable to signal as either IL-1R-like or AcP-like components, suggesting they function as a new class of receptors within this family.
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