通过蛋白质激酶 Akt 调节由内皮衍生的氧化生产
D Fulton1, J P Gratton, T J McCabe
1Department of Pharmacology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Nature
|June 22, 1999
概括
氨酸/氨酸蛋白激酶Akt在氨酸1179上直接化内皮氧化合成酶 (eNOS),激活它并增加氧化 (NO) 的产生. 这一发现将Akt信号与内皮细胞中NO的释放联系起来.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 内皮氧化合成酶 (eNOS) 调节血压,血管改造和血管生成.
- 在氧化 (NO) 生产中,eNOS酸化的作用和负责的激酶在很大程度上是未知的.
研究的目的:
- 研究Akt在酸化和调节eNOS活动中的作用.
- 通过Akt识别eNOS酸化的特定部位及其功能后果.
主要方法:
- 使用Akt和eNOS进行体外激酶试验.
- eNOS (S1179A突变体) 的位点定向突变发生.
- 腺病毒介导的基因转移以调节内皮细胞中的Akt活性.
主要成果:
- 阿克特在1179处直接酸化eNOS,从而激活酶并增加NO的产生.
- 一种突变的eNOS (S1179A) 能够抵抗Akt介导的酸化和激活.
- 激活的Akt增强了基底NO释放,而抑制的Akt则减少了血管内皮生长因子刺激的NO生产.
结论:
- eNOS是Akt的新型基质,在Akt信号和NO生产之间建立了直接联系.
- 在S1179的eNOS的Akt介导酸化是内皮细胞中NO释放的关键调节机制.
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