Identification of two regions within the cytoplasmic domain of the human interferon-gamma receptor required for function.
Functionally active human interferon-gamma (IFN gamma) receptors require the presence of at least two polypeptides: the IFN gamma receptor and an accessory molecule encoded by a gene on human chromosome 21. Here we have used a murine L cell line that stably contains human chromosome 21 (SCC16-5) to determine whether the receptor's cytoplasmic domain is important for receptor function. SCC16-5 stably transfected with the full-length human IFN gamma receptor cDNA bound, internalized, and responded to human IFN gamma. In contrast, SCC16-5 expressing human IFN gamma receptors lacking a cytoplasmic domain bound human IFN gamma but did not internalize or respond to it. Using a family of IFN gamma receptor deletion mutants, two functionally important regions within the intracellular domain were identified: (a) a membrane proximal region (residues 256-303) required for ligand processing and biologic responsiveness and (b) the carboxyl-terminal 39 amino acids (residues 434-472) needed exclusively for biologic responses.
Farrar
M A
MA
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Fernandez-Luna
J
J
Schreiber
R D
RD
D000818:Animals; D001483:Base Sequence; D002891:Chromosomes, Human, Pair 21; D004247:DNA / Q000235:genetics; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D006801:Humans; D007372:Interferons / Q000378:metabolism / Q000494:pharmacology; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D011971:Receptors, Immunologic / Q000235:genetics*; D017471:Receptors, Interferon; D011994:Recombinant Proteins / Q000235:genetics; D014162:Transfection
D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D004247:DNA; D007372:Interferons