Identification of two regions within the cytoplasmic domain of the human interferon-gamma receptor required for function.
Identification of two regions within the cytoplasmic domain of the human interferon-gamma receptor required for function.
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DOI：
10.1016/s0021-9258(18)55039-0
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发表时间：
1991-10
期刊：
影响因子：
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通讯作者：
Michael A. Farrar;J. Fernández-Luna;R. D. Schreiber
中科院分区：
文献类型：
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作者：
Michael A. Farrar;J. Fernández-Luna;R. D. Schreiber
功能活跃的人类干扰素γ (IFN γ)受体需要至少两种多肽的存在：干扰素γ受体和由人类21号染色体上的一个基因编码的辅助分子。在这里，我们使用稳定含有人类21号染色体（SCC16-5）的小鼠L细胞系来确定受体的细胞质结构域对受体功能是否重要。SCC16-5稳定转染全长人IFN γ受体cDNA结合，内化，并响应人IFN γ。相比之下，表达人IFN γ受体的SCC16-5缺乏与人IFN γ结合的细胞质结构域，但不内化或对其产生反应。利用IFN γ受体缺失突变体家族，鉴定了细胞内两个功能重要的区域：(a)配体加工和生物反应所需的膜近端区域（残基256-303）和(b)生物反应只需要羧基末端39个氨基酸（残基434-472）。
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.