Аннотация:The mitogenic effect of growth factors is mediated by the transcriptional regulation of numerous genes which control cell cycle progression and DNA replication. In addition, in order to realize the mitogenic signal into functional response, genes involved in proliferation-related biochemical and physiological processes are co-regulated. In this study, we show that in mitogen-stimulated human blood lymphocytes, enhanced ouabain-sensitive Rb+(K+) fluxes in the middle/late stage of G0/G1/S transit are associated with the increased number of Na+,K+ pumps expressed at the cell surface (as determined by the [3H]ouabain binding). Analysis of total RNA (RT-PCR) and protein abundance (Western blotting) showed a 3-fold increase in the level of Na+,K+-ATPase α1- and β1-subunits mRNAs and significant increase in the Na+,K+-ATPase α1-subunit protein during the first day of mitogen-induced proliferation. In competent T lymphocytes, recombined interleukin-2 (IL-2) was revealed to increase both the transport activity of Na+/K+ pump and the content of Na+,K+-ATPase α1-protein. The pharmacological inhibition of MEK/ERK or JAK/STAT cascades suppressed the IL-2-induced proliferation and reduced the functional and protein expressions of Na+,K+-ATPase. These results suggest that in mitogen-induced human blood lymphocytes (1) the functional expression of Na+/K+ pump is closely associated with the cell cycle progression, being dependent on IL-2; (2) the cell cycle-associated enhancement of K+ transport is a result of increased number of newly synthesized functioning Na+/K+ pumps in cell membrane; (3) the cytokine signalling via the IL-2 receptor is necessary for the upregulation of Na+/K+ pump during the lymphocyte transition from quiescence to proliferation.