Phosphorylation-regulated CI− channel in CHO cells stably expressing the cystic fibrosis gene

Phosphorylation-regulated CI− channel in CHO cells stably expressing the cystic fibrosis gene
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DOI:
10.1038/352628a0
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发表时间:
1991-08
期刊:
影响因子:
64.8
通讯作者:
J. Tabcharani;X. Chang;J. Riordan;J. Hanrahan
J. Tabcharani;X. Chang;J. Riordan;J. Hanrahan
中科院分区:
综合性期刊1区
文献类型:
--
作者:
J. Tabcharani;X. Chang;J. Riordan;J. Hanrahan

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当重组病毒1,2感染非上皮细胞表达囊性纤维IS基因时,出现环状AMP刺激的氯离子电导。在该系统中,环状AMP刺激的氯离子电导是由与人分泌上皮细胞2-4相同的欧姆、低电导的氯离子通道介导的,但尚未直接证明该通道受磷酸化的控制。本文报道了囊性纤维IS基因稳定转染中国仓鼠卵巢细胞后出现的低电导氯离子通道。该通道由cAMP的膜途径类似物在细胞内调节,在细胞外由蛋白激酶A和C以及碱性磷酸酶调节。这些结果进一步证明,囊性纤维化跨膜调节因子是一种氯通道,可被特定的磷酸化事件激活,而被去磷酸化失活;它们揭示了汇聚的激酶调节通路之间的意外协同作用。
A CYCLIC AMP-stimulated choride conductance appears when the cystic fibres is gene is expressed in non-epithelial cells by infection with recombinant viruses1,2. Cyclic AMP-stimulated conductance in this system is mediated by the same ohmic, low-conductance Cl-channel as in human secretory epithelia2–4, but control of this channel by phosphorylation has not been directly demonstrated. Here we report the appearance of the low-conductance Cl-channel in Chinese hamster ovary cells after stable transfection with the cystic fibres is gene. The channel is regulated on-cell by membrane-permeant analogues of cAMP and off-cell by protein kinases A and C and by alkaline phosphatase. These results are further evidence that the cystic fibrosis transmembrane regulator is a Cl-channel which can be activated by specific phosphorylation events and inactivated by dephosphorylation; they reveal an unsuspected synergism between converging kinase regulatory pathways.