Cloning of a novel receptor subunit, AcPL, required for interleukin-18 signaling.
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 NFkappaB. Interleukin-18 (interferon-gamma-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 NFkappaB 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 vitro immunoprecipitation 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.
Born
T L
TL
Immunex Corporation, Seattle, Washington 98101, USA. tborn@immunex.com
Thomassen
E
E
Bird
T A
TA
Sims
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D053728:Interleukin-18 Receptor beta Subunit; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D018076:DNA, Complementary; C115629:IL18RAP protein, human; D007375:Interleukin-1; D020382:Interleukin-18; D053728:Interleukin-18 Receptor beta Subunit; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1