Аннотация:The aim of the study was to elucidate the mechanism responsible for the proliferation-related regulation of Na,K-ATPase pump. Our data demonstrate 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-ATPase pumps expressed at the cell surface (as determined by the [3H]ouabain binding). Analysis of total RNA (RT-PCR) and protein (Western blotting) showed a 3-fold increase in the level of Na,K-ATPase α1-subunit and β1-subunit mRNAs and significant increase in the Na,K-ATPase α1-subunit protein during the first day of mitogen-induced proliferation. The elevated K transport as well as the increased expression of Na,K-ATPase is closely associated with the IL-2-dependent stage of T cell response. The pharmacological inhibition of IL-2-induced MEK/ERK or JAK/STAT cascades suppressed the IL-2-induced proliferation and reduced the functional and protein expressions of Na,K-ATPase. It is concluded that during the lymphocyte transition from resting stage to proliferation (1) long-term activation of Na,K-ATPase pump is due to the enhanced expression of Na,K-ATPase protein and mRNA, and (2) the cytokine signalling via the IL-2 receptor is necessary for the cell cycle-associated upregulation of Na,K-ATPase.