Activation of the C‐fos promoter by increased internal pH

Changes in intracellular pH (pHin) take part in the mitogenic response. Their importance has been stressed by the finding that mouse fibroblasts expressing a yeast proton pumping ATPase (PMA1) exhibit a transformed phenotype and are tumorigenic. These cells do maintain a higher pHin, supporting the idea that elevated pHin may act as a proliferative trigger. Here we show that cells constitutively expressing PMA1 have higher levels of the AP-1 transcription factor. The use of stable transfectants and transient transfection assays show that PMA1 activity induces transactivation of the c-fos promoter. The activation of the promoter is mediated throughout the serum response element (SRE). The use of protein kinase C inhibitors suggests that AP-1 activation is achieved through a pathway independent of protein kinase C.