lysophosphatidate诱导的细胞增殖:识别和剖析由G蛋白介导的信号通路
E J van Corven1, A Groenink, K Jalink
1Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.
Lysophosphatidic 酸 (LPA) 通过涉及Gi 蛋白的百日咳毒素敏感通路刺激纤维细胞增殖. 这种信号传递与激活蛋白激酶C的通路不同,这表明LPA在G蛋白信号传递中的新角色.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 信号传输 信号传输
背景情况:
- lysophosphatidic 酸 (LPA) 是一种简单的脂,已知对静止纤维细胞具有线性作用.
- 由LPA诱导的细胞增殖是独立于其他线粒激素的,对百日咳毒素敏感.
研究的目的:
- 阐明在纤维细胞中介于LPA诱导的线粒发生的特定信号通路.
- 为了区分由LPA激活的各种G蛋白结合通路的作用.
主要方法:
- 咳毒素治疗,以评估Gi蛋白的参与.
- 测量氨酸化物水解和Ca2+调动.
- 阿拉基酸释放的分析.
- 对腺酸环酶活性的评估.
- 与布拉迪基宁信号进行比较.
主要成果:
- LPA至少激活了三个不同的信号级联:酸化水解 (对咳毒素不敏感),酸释放 (依赖GTP) 和腺酸环酶抑制 (对咳毒素敏感的Gi蛋白).
- 布拉迪基宁模仿了前两个LPA反应,但不激活Gi或刺激DNA合成.
- 氨酸酸解-蛋白激酶C通路对于LPA诱导的线粒发生并非必不可少.
结论:
- 纤维细胞中LPA诱导的线粒发生主要由百日咳毒素敏感的Gi蛋白通路介导.
- 对于LPA驱动的细胞增殖,类化物水解途径既不需要,也不够.
- LPA和相关的脂可能在G蛋白介导的信号传导中发挥着新的作用.
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