Cloning of a Novel Receptor Subunit, AcPL, Required for Interleukin-18 Signaling

• Published in: The Journal of biological chemistry Vol. 273; no. 45; pp. 29445 - 29450
• Main Authors: Born, Teresa L., Thomassen, Elisabeth, Bird, Timothy A., Sims, John E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.11.1998; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Cloning, Molecular; COS Cells; DNA, Complementary; Humans; Interleukin-1 - metabolism; Interleukin-18 - metabolism; Interleukin-18 Receptor beta Subunit; Mice; Molecular Sequence Data; Protein Binding; Receptors, Interleukin; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - metabolism; Sequence Homology, Amino Acid; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.45.29445

We have identified a novel member of the interleukin-1 (IL-1) receptor family, which we have termed AcPL. In transient transfection assays, we were unable to demonstrate a role for AcPL in IL-1-induced activation of NFκB. Interleukin-18 (interferon-γ-inducing factor) is another member of the IL-1 family of cytokines, and it has recently been shown that IL-18 has a weak affinity for IL-1R-rp1. We examined whether AcPL might function alone or in concert with IL-1R-rp1 to mediate IL-18 signaling. We found that both IL-1R-rp1 and AcPL expression were required for induction of NFκB activity and for activation of c-Jun N-terminal kinase in response to IL-18. Furthermore, a dominant negative version of AcPL specifically inhibited IL-18 signaling. In vitroimmunoprecipitation assays demonstrated that AcPL alone was unable to bind IL-18 with any appreciable affinity. We propose that although IL-1R-rp1 binds the cytokine, IL-1R-rp1 and AcPL proteins are both required for IL-18 signaling, analogous to the requirement for both IL-1R and IL-1RAcP in IL-1-mediated responses.