通过Gi-蛋白β-玛子单元激素刺激腺酸环酶的激素刺激
A D Federman1, B R Conklin, K A Schrader
1Department of Pharmacology, University of California San Francisco 94143.
Nature
|March 12, 1992
概括
抑制性G蛋白 (Gi) 的β玛子单元可以刺激循环AMP (cAMP) 合成. 这种情况是有条件的,需要由αs-GTP共同刺激,并激活腺环酶II,从而揭示出一种新的信号作用.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 生物化学 生物化学
背景情况:
- 与G蛋白结合的受体通过激活异构三基G蛋白来启动信号级联.
- 通常情况下,G蛋白的α子单元向下游效应器传输信号.
- 新出现的证据表明,β 玛子单元也可能在效应器通路中发挥调节作用.
研究的目的:
- 调查G蛋白β-玛子单元在调节腺环酶活性中的潜在作用.
- 为了确定抑制性G蛋白 (Gi) 的β-玛子单元是否可以调节循环AMP (cAMP) 合成.
- 在细胞反应中阐明Giβ玛子单元的新信号功能.
主要方法:
- 在哺乳动物细胞中,突变活跃的alpha s与adenylyl cyclase II的同时表达.
- 使用百日咳毒素来禁用Gi蛋白.
- 采用转化素的α子单元作为β玛清除剂.
主要成果:
- 通过抑制受体 (Gi-合) 作用的激动剂在与活性αs和adenylyl cyclase II一起表达时刺激了cAMP合成.
- 证据表明,Giβ玛子单元调解了这种依赖于β玛的腺酸环酶II的激发.
- 这种刺激是有条件的,需要β-玛子单元和α-s-GTP来激活乙烯基基环酶II.
结论:
- 基蛋白的β玛子单元具有一种新的信号功能:条件刺激cAMP合成.
- 这一途径涉及依赖alpha s-GTP的方式激活adenylyl cyclase II.
- 这些发现扩大了我们对G蛋白信号传递的理解,超出了α子单元的规范作用.
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