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首页> 外文期刊>Molecular and Cellular Biology >Transformation and pH homeostasis of fibroblasts expressing yeast H(+)-ATPase containing site-directed mutations.
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Transformation and pH homeostasis of fibroblasts expressing yeast H(+)-ATPase containing site-directed mutations.

机译:表达酵母H(+)-ATPase包含定点突变的成纤维细胞的转化和pH稳态。

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Mouse fibroblasts expressing a yeast proton-pumping ATPase show tumorigenic transformation (R. Perona, and R. Serrano, Nature (London) 334:438-440, 1988). By expressing site-directed mutations of the yeast ATPase with different levels of activity, a close correlation has been found between enzyme activity, tumorigenic transformation, and intracellular pH measured by weak-acid distribution. Fibroblasts expressing the yeast proton-pumping ATPase showed increased capability to grow at acidic pH and to resist lethal acidification mediated by reversal of the Na(+)-H+ antiporter. Measurements with microelectrodes in individual cells demonstrated electrical hyperpolarization and confirmed the increased pH of cells expressing yeast ATPase. These results indicate that the yeast enzyme expressed in mouse fibroblasts has electrogenic proton-pumping activity and that this activity deregulates fibroblast growth. This suggests a connection between the biophysical phenomena of proton transport, intracellular pH, and membrane potential and the biochemical regulatory circuits based on protein kinases and transcription factors.
机译:表达酵母质子泵ATP酶的小鼠成纤维细胞显示出致瘤转化(R.Perona和R.Serrano,Nature(伦敦)334:438-440,1988)。通过表达具有不同活性水平的酵母ATPase的定点突变,已发现酶活性,致瘤转化和通过弱酸分布测量的细胞内pH值之间具有密切的相关性。表达酵母质子泵ATPase的成纤维细胞显示出在酸性pH下生长和抵抗由Na(+)-H +反向转运体逆转介导的致死酸化的能力增强。在单个细胞中用微电极进行的测量显示出电超极化,并证实表达酵母ATPase的细胞的pH升高。这些结果表明,在小鼠成纤维细胞中表达的酵母酶具有电质子泵浦活性,并且该活性使成纤维细胞的生长失调。这表明质子转运,细胞内pH和膜电位的生物物理现象与基于蛋白激酶和转录因子的生化调节回路之间存在联系。

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