Summary
Cultured ARL15 cells respond to abnormally low extracellular K+ concentrations by increasing the abundance of Na,K-ATPase (the Na/K pump). This response is preceded by significant increases in the mRNAs of the α1 and β1 subunits of this enzyme, implying transcriptional or post-transcriptional regulation in the response. The present study concerned the possible participation of serum factors in low K+ induction of Na,K-ATPase.
In normal K+ (4.5 mm) or low K+ (0.68 mm) the presence of 10% calf serum had no effect on Na,K-ATPase activity. The serum independence of the response to low K+ raised the possibility that low K+ may itself elicit a “growth” response. Accordingly, the effect of low K+ on mRNA abundances of four protooncogenes (c-fos, c-myc, c-jun and c-ski) was evaluated in the early phase of the response by quantitative Northern blot analysis. The mRNA for c-fos was transiently elevated by low K+, with a peak at 30 min. In contrast, low K+ had no measurable effect on the abundances of c-myc, c-jun and c-ski, for up to 2 hr of exposure.
The early elevation of c-fos mRNA makes it a candidate mediator in this signal-transduction pathway. Induction of c-fos mRNA by the phorbol ester, PMA, or by dioctanoyl glycerol, however, had no effect on Na,K-ATPase activity. These results indicate that an increase in c-fos mRNA alone is not sufficient to induce Na,K-ATPase. Whether induction of c-fos is necessary for the response to low K+ remains to be determined in future studies.
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Financial support for this study was provided by NIH-GM36618.
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Cayanis, E., Russo, J.J., Wu, Ys. et al. Serum independence of low K+ induction of Na,K-ATPase: Possible role of c-fos . J. Membarin Biol. 125, 163–170 (1992). https://doi.org/10.1007/BF00233355
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DOI: https://doi.org/10.1007/BF00233355