Functional characterization of a hybrid human-mouse interferon gamma receptor: evidence for species-specific interaction of the extracellular receptor domain with a putative signal transducer.
The human interferon gamma (IFN-gamma) receptor expressed in mouse cells displays binding properties indistinguishable from those of the resident receptor on human cells. Still, mouse cells expressing the human IFN-gamma receptor remain insensitive to human IFN-gamma. It is widely accepted that at least one species-specific cofactor encoded within human chromosome 21 is required for signal transduction. To define structural domains of the human IFN-gamma receptor responsible for this species-specific interaction, a hybrid between the human and the murine receptor was constructed and expressed in mouse L929 cells or in mouse L cell-derived SCC16-5 cells, which contain human chromosome 21. This hybrid receptor, which consisted of the extracellular domain of the human IFN-gamma receptor and the transmembrane and cytoplasmic domains of the murine IFN-gamma receptor, was found to bind human IFN-gamma with high affinity. However, only SCC16-5 cells expressing the human/mouse hybrid receptor were responsive to human IFN-gamma as revealed by enhanced expression of major histocompatibility complex class I antigens, induction of the transcription factor IRF-1, and induction of a partial antiviral state. These findings strongly suggest that IFN-gamma-mediated signal transduction requires a species-specific interaction of the extracellular portion of the known ligand-binding IFN-gamma receptor chain with an additional, presumably membrane-anchored receptor subunit.
Hemmi
S
S
Institute of Molecular Biology I, University of Zürich, Switzerland.
Merlin
G
G
Aguet
M
M
D000818:Animals; D002891:Chromosomes, Human, Pair 21; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells; D007371:Interferon-gamma / Q000494:pharmacology*; D007739:L Cells; D046911:Macromolecular Substances; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000502:physiology*; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D014762:Viral Interference
D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D007371:Interferon-gamma