通过支架蛋白Shc1对EGF信号网络的时间调节
Yong Zheng1, Cunjie Zhang, David R Croucher
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto M5G 1X5, Canada.
Nature
|July 13, 2013
概括
在EGF刺激后,Shc1支架蛋白通过不同的酸化事件和蛋白质相互作用来指导信号传递. 它从促进细胞生长转向调节细胞入侵和形状.
科学领域:
- 细胞生物学 细胞生物学
- 分子信号传递是分子信号传递.
- 蛋白质的生物化学 蛋白质的生物化学
背景情况:
- 细胞表面受体利用支架蛋白来招募细胞质点,这种机制的确切功能尚不清楚.
- 受体氨酸激酶 (RTK) 激活像Shc1这样的支架,这些支架具有氨酸结合 (PTB) 域,对于下游信号传输至关重要.
- 了解脚手架蛋白质动态是解读复杂细胞通信网络的关键.
研究的目的:
- 阐明Shc1支架蛋白对表皮生长因子 (EGF) 刺激的动态反应.
- 为了识别控制Shc1功能的顺序酸化事件和蛋白质相互作用.
- 确定Shc1在时间信号流和路径切换中的作用.
主要方法:
- 使用定量质谱分析了EGF刺激后的Shc1酸化和蛋白质相互作用.
- 时间解析分析捕获了与Shc1.1结合蛋白质的独特波浪.
- 功能性测试评估了Shc1-介导信号对细胞过程的影响.
主要成果:
- 在EGF刺激时,Shc1经历了多个波的酸化和蛋白质相互作用.
- 起初,Shc1通过Grb2适配器与色胺位结合,招募激活益菌原/生存通路的蛋白质.
- 随后,Akt介导的酸化招募Ptpn12,它将Shc1切换到SgK269介导的途径,调节细胞入侵和形态发生.
结论:
- 在EGF刺激后,Shc1支架蛋白作为信号转导时间的关键调节者.
- Ptpn12充当分子开关,将Shc1信号从促进生长的途径转换为调节细胞形态的途径.
- Shc1的动态相互作用调节信息的时间流,影响各种细胞功能.
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