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Título: | Transformation and pH homeostasis of fibroblasts expressing yeast H(+)-ATPase containing site-directed mutations |
Autor: | Perona Abellón, Rosario CSIC ORCID; García del Portillo, Francisco CSIC ORCID ; Giráldez, Fernando; Serrano, Ramón CSIC ORCID | Fecha de publicación: | 1990 | Editor: | American Society for Microbiology | Citación: | Molecular and Cellular Biology 10(8): 4110-4115 (1990) | Resumen: | 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 fibroblast 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. | URI: | http://hdl.handle.net/10261/78925 | DOI: | 10.1128/MCB.10.8.4110 | Identificadores: | doi: 10.1128/MCB.10.8.4110 issn: 0270-7306 e-issn: 1098-5549 |
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