Signaling steps involving the cytoplasmic domain of the interferon-gamma receptor alpha-subunit are not species-specific.
The ligand-binding chain of the interferon-gamma receptor (IFN-gamma R) is a unique cell surface protein which has no similarities to other cytokine receptors. Expression of this receptor chain (alpha-subunit) is not sufficient to mediate responsiveness to IFN-gamma. We and others have shown that IFN-gamma-mediated signal transduction requires a species-specific interaction of the extracellular portion of the known IFN-gamma receptor alpha-chain with an additional receptor subunit that was cloned recently and designated IFN-gamma R beta-chain or accessory factor 1. Here, we investigated whether this tight species barrier also applies to signaling events mediated by the cytoplasmic receptor domain. A cell line derived from embryos that lack the IFN-gamma R alpha-subunit was reconstituted with a hybrid mouse-human alpha-subunit that consisted of an extracellular murine and transmembrane and cytoplasmic human domains. The experiments reported herein showed that in mouse cells, the human intracellular domain of the hybrid IFN-gamma R alpha-subunit was fully functional and that, therefore, signaling steps involving this domain are not species-specific.
Böhni
R
R
Institute of Molecular Biology I, University of Zürich, Switzerland.
Hemmi
S
S
Aguet
M
M
D000818:Animals; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D046911:Macromolecular Substances; D051379:Mice; D055503:Protein Multimerization; D012333:RNA, Messenger / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping; D015398:Signal Transduction; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D046911:Macromolecular Substances; D012333:RNA, Messenger; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor