由生长因子受体激活的多种信号通路诱导广泛的重叠,而不是独立的基因组
D Fambrough1, K McClure, A Kazlauskas
1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Cell
|June 25, 1999
概括
受体氨酸激酶 (RTK) 途径在诱导直接早期基因 (IEG) 方面广泛重叠. 特定的途径突变显示出不同的基因诱导模式,影响细胞反应.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 基因表达分析 基因表达分析
背景情况:
- 受体氨酸激酶 (RTK) 是关键的细胞表面受体,通过下游信号通路调节各种细胞过程.
- 直接早期基因 (IEGs) 是快速和暂时激活的基因,在细胞对外部刺激的反应中发挥关键作用.
- 了解RTK信号传导和IEG诱导之间的相互作用对于破译细胞可塑性和反应机制至关重要.
研究的目的:
- 研究激活受体氨酸激酶 (RTK) 信号通路与直接早期基因 (IEG) 的转录诱导之间的关系.
- 为了确定负责诱导纤维细胞IEGs的特定RTK激活通路.
- 为了比较纤维细胞中不同RTK的IEG诱导概况.
主要方法:
- 全球基因表达监测使用转录组分析.
- 使用突变的血小板衍生生生长因子β受体 (PDGFRbeta) 构造缺乏特定信号通路结合位点 (PLCgamma,PI3K,SHP2,RasGAP,Grb2).
- 通过PDGFRbeta和纤维细胞生长因子受体1 (FGFR1) 诱导IEG的比较分析.
主要成果:
- 鉴定了66个由PDGFRbeta信号诱导的纤维细胞IEG.
- 缺少PLCgamma,PI3K,SHP2和RasGAP结合部位的突变PDGFRbeta受体保留了部分诱导64种IEG的能力,这表明重叠的途径效应.
- 移除Grb2结合部位显著减少了IEG诱导,突出了其广泛的重要性.
- 一种恢复RasGAP结合部位的PDGFRbeta突变诱导了一组独特的干扰素反应基因.
- 在纤维细胞中,PDGFRbeta和FGFR1诱导的IEG基本相同.
结论:
- 多个RTK激活的信号通路对IEG诱导产生广泛的重叠效应.
- 在RTK路径中的特定信号组件有助于诱导不同的基因组,影响细胞反应.
- PDGFRbeta和FGFR1信号通路汇聚在纤维细胞中诱导类似的直接早期基因组.
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