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mTOR Ser1261是一种AMPK依赖的酸盐,在小鼠和人类骨肌中不需要mTORC2活动
Jingwen Li1,2, Agnete B Madsen1, Jonas R Knudsen1
1August Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
运动,而不是胰岛素,通过AMPK激活骨肌肉中的mTOR Ser1261酸化. 这个网站这个网站.
科学领域:
- 细胞代谢和信号通路的发生.
- 肌肉生理学和运动科学
背景情况:
- AMP激活蛋白激酶 (AMPK) 和拉巴胺素的机械标 (mTOR) 是细胞生长和新陈代谢的关键调节者.
- 在mTORC1和mTORC2复合体中存在的mTOR在细胞过程中起着至关重要的作用.
- 建议mTOR在Serine 1261 (Ser1261) 的酸化受胰岛素和AMPK的影响,可能作为一个融合点.
研究的目的:
- 为了研究mTOR Ser1261酸化在骨肌肉中的调节和功能.
- 为了确定Ser1261是否作为胰岛素和AMPK信号在肌肉中的融合点.
- 阐明Ser1261酸化在mTORC1和mTORC2复合体中的作用.
主要方法:
- 利用了人类运动研究,转基因小鼠模型 (包括猛龙肌肉淘汰/过度表达和酶死亡的AMPK模型) 和HEK293细胞培养.
- 评估mTOR Ser1261酸化作为对胰岛素和收缩活性的反应.
- 研究了基因修饰对mTORC1和mTORC2基质酸化的影响.
主要成果:
- mTOR Ser1261酸化并未受到胰岛素的刺激,但以AMPK依赖的方式对肌肉收缩活动产生了急性反应.
- 收缩刺激的Ser1261酸化被猛禽水平调节,表明mTORC1.1的参与.
- 具有mTOR Ser1261Ala突变的HEK293细胞显示mTORC1基质酸化受损,但mTORC2基质酸化没有受损.
- 缺少可检测的Ser1261酸化的肌肉特异性激酶死亡的AMPK小鼠没有显示mTORC1或mTORC2活性的变化.
结论:
- mTOR Ser1261是一种运动响应的,在骨肌肉中的AMPK依赖的酸,独立于胰岛素.
- 在Ser1261的酸化似乎主要发生在骨肌肉中的mTORC1复合体内.
- 虽然Ser1261受到AMPK的调节,但在这种情况下,它对于mTORC1或mTORC2活动并不重要.
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