Szente B E, Soos J M, Johnson H W
Department of Microbiology, University of Florida, Gainesville 32611.
Biochem Biophys Res Commun. 1994 Sep 30;203(3):1645-54. doi: 10.1006/bbrc.1994.2375.
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.
我们之前已经表明，小鼠干扰素γ（IFNγ）及其C末端肽muIFNγ（95 - 133）与合成肽MIR（253 - 287）中所含的IFNγ受体细胞质结构域上的一个区域结合。小鼠受体的这个区域与其人类对应区域具有相当高的同源性（约80%）。在此我们报告，不仅人类IFNγ及其人类IFNγ C末端肽huIFNγ（95 - 134）与人类IFNγ受体的细胞质结构域结合，而且这种相互作用是种属非特异性的。muIFNγ（95 - 133）与人类IFNγ受体细胞质肽HIR（252 - 291）结合，而huIFNγ（95 - 133）与MIR（253 - 287）结合。此外，用小鼠或人类IFNγ的C末端肽处理小鼠巨噬细胞系会导致MHC II类分子表达上调10倍，并增加对水泡性口炎病毒（VSV）感染的抵抗力（产量降低10^6 - 10^9倍）。这些数据表明IFNγ的C末端在细胞内信号传导过程的启动中具有直接作用，并且可能暗示细胞外信号分子的一种更普遍的作用机制。
