人类肌管中的生长因子对AKT异型的差异激活
Brandon M Roberts1, Alyssa V Geddis1, Ronald W Matheny1,2
1US Army Research of Environmental Medicine, Natick, Massachusetts, USA.
Physiological reports
|October 25, 2023
概括
这项研究确定AKT1是人类骨肌细胞中最丰富的AKT异型. 胰岛素和IGF-I不同化AKT异型,AKT1表现出不同的模式,这表明它在骨肌肉生理学中的关键作用.
科学领域:
- 肌肉生理学 肌肉生理学
- 细胞信号传递 细胞信号传递
- 分子生物学分子生物学
背景情况:
- AKT信号通路对肌肉功能至关重要,由胰岛素,生长因子和运动激活.
- 哺乳动物有三种AKT异型 (AKT1,AKT2,AKT3) 具有重叠和独特的作用.
- 有限的知识存在于AKT异型丰富度和激活由胰岛素/IGF-I在人类骨肌肉.
研究的目的:
- 为了确定AKT异型在人类骨初级髓管中的相对丰度.
- 研究AKT异型体在对胰岛素和IGF-I刺激的反应中激活的模式.
- 为了阐明人类骨肌肉中AKT异型的差异酸化.
主要方法:
- 从原始人类骨肌管中获取的蛋白质溶解物被使用液体染色学-并行反应监测/质谱分析,以量化AKT异型丰度.
- 用胰岛素 (100nM) 或IGF-I (10nM) 在不同时间点 (5,20,45,60分钟) 刺激肌管.
- 测量了AKT异型和泛AKT的酸化水平,以评估激活.
主要成果:
- AKT1是最丰富的异型,而AKT3在人类骨肌管中最少.
- 胰岛素显著增加了AKT1和AKT2的酸化,但并没有增加AKT3.
- 在所有时间点上,IGF-I显著增加了泛-AKT的酸化.
- 在特定时间点进行胰岛素和IGF-I刺激后,AKT1的酸化明显高于AKT2和AKT3.
结论:
- AKT1是人类骨髓管中占主导地位的AKT异型.
- 胰岛素和IGF-I诱导AKT异形的差异酸化,突出异形特异性反应.
- AKT异构体的独特酸化模式,特别是AKT1,可能解释其在骨肌肉中的调节作用.
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