通过cAMP依赖蛋白激酶对R域的酸化调节了CFTR化通道
S H Cheng1, D P Rich, J Marshall
1Genzyme Corporation, Framingham, Massachusetts 01701.
Cell
|September 6, 1991
概括
囊性纤维化转膜导电调节器 (CFTR) 蛋白质的酸化调节化道活性. 对于这种cAMP介导的调节,四个关键的血清位点是必不可少的,这表明了涉及R域的机制.
科学领域:
- 分子生物学分子生物学
- 细胞生理学 细胞生理学
背景情况:
- 囊性纤维化跨膜导电调节器 (CFTR) 蛋白质是对表皮功能至关重要的化物通道.
- 通过酸化调节CFTR活性,特别是对循环AMP (cAMP) 的反应.
研究的目的:
- 通过蛋白激酶A (PKA) 在CFTR上确定特定的体内酸化位.
- 研究这些酸化部位在调节CFTR化道活性中的功能作用.
主要方法:
- 在CFTR上识别的血清残留物的位点定向突变发生.
- SPQ光测定用于测量化物 (Cl-) 通道活性.
- 在突变发生后对cAMP响应道功能的分析.
主要成果:
- 四种血清残留物 (660,737,795,813) 被确定为体内PKA酸化标.
- 个别部位的突变发生并没有取消Cl-通道活性.
- 四个部位同时发生突变,取消了cAMP刺激的Cl-通道活性.
- 酸化似乎以静电驱逐调节R域,使Cl-通道成为可能.
结论:
- 已确定的四个血清酸化位是退化的,但它们对于cAMP介导的CFTR通道调节是集体必不可少的.
- 通过PKA对CFTR的酸化可能缓解R域的抑制,促进化物运输.
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