增长因子受体在哺乳动物UVC反应中的参与
C Sachsenmaier1, A Radler-Pohl, R Zinck
1Kernforschungszentrum Karlsruhe, Institut für Genetik, Federal Republic of Germany.
Cell
|September 23, 1994
概括
短波长紫外线 (UVC) 通过细胞质信号传递激活HeLa细胞中的转录因子和基因. 这种UVC反应涉及生长因子受体,并通过阻断它们的信号通路来抑制.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 辐射生物学 辐射生物学
背景情况:
- 短波长紫外线 (UVC) 是一个已知的细胞压力.
- 细胞对紫外线的反应涉及复杂的信号通路.
- 像AP-1和TCF/Elk-1这样的转录因子在基因调节中起着至关重要的作用.
研究的目的:
- 研究HeLa细胞对紫外线辐射的反应背后的分子机制.
- 识别参与UVC诱导基因激活的信号通路和细胞组件.
- 探索生长因子受体在调解细胞对紫外线反应中的作用.
主要方法:
- 用UVC对HeLa细胞进行辐射.
- 对转录因子激活的分析 (AP-1,TCF/Elk-1).
- 对c-fos和c-jun的基因表达的评估.
- 研究细胞质信号转导通路 (Ras,Raf,MAP激酶).
- 使用生长因子 prestimulation,suramin 和主导阴性EGF受体突变的抑制研究.
- 对表皮生长因子 (EGF) 受体氨酸酸化的分析.
主要成果:
- 紫外线辐射诱导AP-1和TCF/Elk-1转录因子的修饰和激活.
- 蛋白质合成独立的c-fos和c-jun基因的转录激活发生在UVC后.
- 紫外线反应由细胞质信号传递介导,涉及Ras,Raf,Src和MAP激酶.
- 紫外线诱导的信号被低调增长因子受体信号,苏拉明或主导负的EGF受体突变体抑制.
- 紫外线照射会导致EGF受体的即时,胺抑制的氨酸酸化.
结论:
- 增长因子受体信号通路在调解细胞对紫外线反应方面具有关键作用.
- 紫外线通过细胞质信号传导级联作用,这些级联与生长因子受体通路相互连接.
- EGF受体是UVC反应的关键组成部分,在照射时经历快速的铁酸化.
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