胰岛素刺激的GLUT4转位需要CAP依赖的TC10激活
S H Chiang1, C A Baumann, M Kanzaki
1Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, Michigan 48105, USA.
Nature
|April 20, 2001
概括
胰岛素通过将GLUT4载体移动到细胞表面来刺激葡萄糖的吸收. 涉及Cbl,CrkII-C3G和TC10的新途径与PI(3)K一起工作,以实现这一必不可少的过程.
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.
- 代谢调节 代谢调节 代谢调节
背景情况:
- 胰岛素介导的葡萄糖吸收依赖于GLUT4运输体转移到肌肉和脂肪组织中的细胞表面.
- 虽然GLUT4囊泡贩运已被理解,但将胰岛素受体激活与转位联系起来的特定信号通路仍然不清楚.
- 对于GLUT4转位,酸-3-OH激酶 (PI(3) K) 的激活是必要的,但不足以实现.
研究的目的:
- 阐明激活胰岛素受体下游的信号通路,该通路介导GLUT4转位.
- 研究Cbl,CrkII-C3G复合体和TC10在胰岛素刺激的葡萄糖摄取中的作用.
- 为了确定这种途径如何与PI(3) K信号交互.
主要方法:
- 研究了通过胰岛素刺激的Cbl氨酸酸化及其通过CAP通过胰岛素受体的招募.
- 分析了Cbl,CrkII-C3G复合体和TC10到脂质的转移.
- 评估了Cbl,CrkII-C3G和TC10通路激活对葡萄糖吸收和GLUT4转位的影响.
主要成果:
- 胰岛素刺激的Cbl酸化导致其转移到脂质,招募CrkII-C3G复合体.
- 在脂质中,CrkII-C3G复合体会激活小的GTP结合蛋白TC10,独立于PI(3) K.
- 激活TC10对于胰岛素刺激的葡萄糖吸收和GLUT4转位至关重要.
结论:
- 涉及Cbl,CrkII-C3G和TC10的新型信号通路对于胰岛素刺激的GLUT4转位至关重要.
- 这条TC10通路与PI(3) K通路并行运行,完全调节胰岛素对葡萄糖吸收的影响.
- 了解这种途径为代谢调节和糖尿病的潜在治疗点提供了新的见解.
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