Ouabain-induced activity of ERK1/2 and STAT3 in carcinoma A431 cells

We investigated the effects of ouabain in a wide range of concentrations (10(-7) -10(-3) M) on Rb+ (K+) influxes, intracellular content of K+ and Na+, and on the tyrosine phosphorylation of STAT1, STAT3, ERK1/2, and of the EGF receptor in human carcinoma A431 cells. Ouabain (10(-5)-10(-7) M) increased the phosphorylation levels of ERK1/2, transcription factor STAT3 (but not STAT1), and of the EGF receptor. Maximum phosphorylation increase was reached 5 min after the ouabain application. The activation of signalling molecules was observed at low concentrations of ouabain. at which neither the Na+/K+-pump transport activity nor the intracellular contents of monovalent cations were altered. An inhibitor of Src-kinases (CGP77675) prevented the ouabain-induced activation both of the EGF receptor and of ERK1/2 and STAT3, suggesting the involvement of the EGF receptor and Src-kinases in the activation of MAPK- and STAT-signalling pathways in ouabain-treated carcinoma A431 cells.