The C-terminus of IFN gamma is sufficient for intracellular function.
We have previously shown that murine interferon gamma (IFN gamma) and its C-terminal peptide, muIFN gamma (95-133), bind to a region on the cytoplasmic domain of the IFN gamma receptor contained in the synthetic peptide, MIR(253-287). This region of the murine receptor bears considerable homology (approximately 80%) to its human counterpart. Here we report that not only do human IFN gamma and the human IFN gamma C-terminal peptide, huIFN gamma(95-134), bind to the cytoplasmic domain of the human IFN gamma receptor, but also that this interaction is species non-specific. MuIFN gamma(95-133) binds to human IFN gamma receptor cytoplasmic peptide HIR(252-291), and huIFN gamma(95-133) binds to MIR(253-287). Furthermore, treatment of murine macrophage cell lines with C-terminal peptides of either murine or human IFN gamma results in 10-fold upregulation of MHC class II molecule expression and increased resistance to infection with vesicular stomatitis virus (VSV) (10(6)-10(9)-fold reduction in yield). These data suggest a direct role for the C-terminus of IFN gamma in the initiation of intracellular signalling processes and may be indicative of a more general mechanism of action for extracellular signalling molecules.
Szente
B E
BE
Department of Microbiology, University of Florida, Gainesville 32611.
Soos
J M
JM
Johnson
H W
HW
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D006801:Humans; D007371:Interferon-gamma / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D007700:Kinetics; D007739:L Cells; D007941:Leukemia P388; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D017471:Receptors, Interferon / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D010446:Peptide Fragments; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor