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双特异性激酶DYRK3对应应力颗粒凝结/溶解到mTORC1信号传递
Frank Wippich1, Bernd Bodenmiller, Maria Gustafsson Trajkovska
1Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Cell
|February 19, 2013
概括
细胞压力触发DYRK3激酶,以控制P颗粒稳定性和mTORC1信号传递. 活跃的DYRK3释放被隔离的mTORC1,将液相过渡与细胞信号通路联系起来.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 通过液-液分离的细胞分裂,就像RNA颗粒的形成一样,影响细胞过程和信号传导.
- 精确的分子机制合液体-液体不混合和信号传导尚未完全理解.
研究的目的:
- 阐明在细胞应激过程中连接液体-液体脱离和信号转导的分子机制.
- 研究双特异性激酶DYRK3在调节P粒状结构和mTORC1信号传递中的作用.
主要方法:
- 研究了DYRK3在应力颗粒动态和mTORC1信号传递中的作用.
- 分析了DYRK3在应力颗粒和细胞质之间循环分离,使用其N端低复杂性域和激酶活性.
- 研究了DYRK3活性状态对应力颗粒溶解,mTORC1释放和PRAS40酸化的影响.
主要成果:
- 在细胞应激期间,DYRK3调节P粒状结构和mTORC1信号的稳定性.
- DYRK3在应力颗粒和细胞质之间表现出循环分离,其N端低复杂性域和激酶活性介导.
- 不活跃的DYRK3通过酸化PRAS40.1来稳定应力颗粒和扣留mTORC1;活跃的DYRK3通过酸化PRAS40.1来促进应力颗粒溶解,mTORC1释放和mTORC1活性.
结论:
- DYRK3 通过液相过渡和细胞信号传递,作为细胞质细分之间的关键环节.
- 这种机制凸显了细胞分区的动态变化如何直接调节mTORC1.1.等信号通路.
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