NIH-3T3细胞的stat3介导转化由构成性活性的Q205L Galphao蛋白进行
P T Ram1, C M Horvath, R Iyengar
1Department of Pharmacology, Immunobiology Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. ramp01@doc.mssm.edu
概括
在NIH-3T3细胞中表达非GTPase活性的Galphao亚单元诱导了细胞转化,并通过c-Src激酶活性激活了信号转换器和转录3 (Stat3) 的激活器.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 信号传输 信号传输
背景情况:
- 异构三元核酸结合蛋白 (G蛋白) 在细胞信号传递中起着至关重要的作用.
- G蛋白的α子单元Galphao参与各种细胞过程.
- 调控不当的G蛋白信号传递可以导致细胞转化.
研究的目的:
- 研究一个构成性活跃的Galphao突变体 (Q205L Galphao,Galphao*) 在NIH-3T3细胞转化中的作用.
- 为了阐明Galphao*表达激活的下游信号通路.
- 确定信号传感器和转录3 (Stat3) 和Src家族激酶激活剂在Galphao*介导转换中的参与.
主要方法:
- 在NIH-3T3细胞中表达Q205L Galphao (Galphao*).
- 分析信号传感器和转录3 (Stat3) 的激活器和基因激活蛋白 (MAP) 激酶激活.
- 主导阴性Stat3和Csk (炭基终端Src酶) 的同时表达.
- 评估NIH-3T3细胞转化和c-Src活动.
主要成果:
- 加尔法*表达诱导NIH-3T3细胞转化.
- Galphao*激活了Stat3,但没有MAP激酶1或2.
- 主要阴性Stat3抑制了Galphao*诱导的转化和Stat3激活.
- 加尔表达增加了c-Src活动.
- Csk表达式阻止了Galphao*诱导的Stat3激活.
结论:
- 信号转换器和转录3的激活器 (Stat3) 作为Galphao*的下游效应器.
- 加尔介导的细胞转化取决于Stat3的激活.
- 氨酸激酶c-Src参与了从Galphao*到Stat3.3的信号通路.
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