Serum independence of low K+ induction of Na,K-ATPase: possible role of c-fos.
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 alpha 1 and beta 1 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 proto-oncogenes (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.
Cayanis
E
E
Center for Reproductive Sciences, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Russo
J J
JJ
Wu
Y S
YS
Edelman
I S
IS
D000818:Animals; D001769:Blood; D002460:Cell Line; D003470:Culture Media; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D016762:Genes, fos; D011188:Potassium / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis*; D014158:Transcription, Genetic
D003470:Culture Media; D012333:RNA, Messenger; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium