激活雌激素受体通过通过酸化由米托基因激活蛋白激酶激活
1Department of Agricultural Chemistry, Tokyo University of Agriculture, Japan.
概括
通过MAPK对雌激素受体 (ER) Ser118的酸化对于ER激活功能1 (AF-1) 的活性至关重要. 像Ras-MAPK这样的生长因子信号通路,通过Ser118酸化调节ER活性.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 人类雌激素受体 (ER) 在细胞过程中起着至关重要的作用.
- 激活功能1 (AF-1) 对于ER转录活动至关重要.
- 翻译后的修改,如酸化,调节蛋白质的功能.
研究的目的:
- 研究ER血清残留118 (Ser118) 酸化在ER活性中的作用.
- 为了确定负责Ser118酸化的激酶.
- 阐明ER Ser118酸化所涉及的信号通路及其对转录活性的影响.
主要方法:
- 在体外和体内生物酸化试验.
- 局部定向的突变发生,以产生ER突变 (Ser118到Alanine).
- 记者基因测试测量转录活动.
- 信号通路组件的过度表达 (MAPKK, Ras).
主要成果:
- 化ER Ser118对于充分的AF-1活动至关重要.
- 线素激活蛋白激酶 (MAPK) 酸化ER Ser118在体外和体内.
- 表皮生长因子 (EGF) 和类似胰岛素的生长因子 (IGF) 刺激Ser118酸化.
- 激活Ras-MAPK通路可以增强雌激素和他莫西芬诱导的ER转录活性.
- 一个突变的ER与Ser118中的氨酸没有显示活动的增强.
结论:
- 由MAPK进行ER Ser118酸化是ER AF-1活动的关键调节机制.
- 增长因子信号通路,特别是Ras-MAPK级联,通过Ser118酸化调节ER活性.
- 准Ras-MAPK通路可能会影响ER介导的基因表达.
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