[Il-2-regulated expression of Na+,K(+)-ATPase in activated human lymphocytes].
Expression of Na+,K(+)-ATPase alfal-subunit and of oubain-sensitive rubidium influxes has been investigated in human peripheral blood lymphocytes. Isolated lymphocytes were stimulated by phytogemagglutinin (PHA) or interleukin-2 (IL-2). It has been shown that during the early stage of the PHA-activation the alfal-subunit abundance in the membrane fractions of the human blood lymphocytes does not change, whereas at the late stages of Go-->G1-->S transition (16-48 h) the alfa1 protein content increases. A translation inhibitor cycloheximide was found to prevent the late increase in alfa1-subunit expression. An immunosuppressant cyclosporin A decreases both IL-2-dependent T-lymphocyte progression and alfa1-subunit abundance by 48 h of PHA-induced lymphocyte activation. In the lymphocytes pretreated by PHA in submitogenic concentration (0.8-1.0 microg/ml) exogenous IL-2 (100 U/ml) induces a proliferative response as well as alfal-protein accumulation. A decrease in alfa1-protein accumulation in the presence of specific inhibitors of separate signal transduction pathways enables us to conclude that protein kinases ERK1/2 (MAPK pathway) and JAK3 (JAK-STAT pathway) mediate the IL-2-dependent regulation of Na+,K(+)-ATPase expression during lymphocyte transition from resting stage to proliferation. A correlation between changes in ouabain-sensitive rubidium influxes and the alfal-subunit amount has been demonstrated. It is concluded that IL-2-dependent-progression of normal human lymphocytes from quiescence to proliferation is accompanied by the increase in Na+,K(+)-ATPase alfa1-subunits expression, and the enhanced transport activity of a sodium pump during the prereplicative stage is provided by the increased number of functional pump units in plasma membrane.
Karitskaia
I A
IA
Aksenov
N D
ND
Vinogradova
T A
TA
Marakhova
I I
II
D002455:Cell Division; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D016623:Ion Pumps; D053616:Janus Kinase 3; D007963:Leukocytes, Mononuclear; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012413:Rubidium / Q000037:antagonists & inhibitors / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D015854:Up-Regulation
D007376:Interleukin-2; D016623:Ion Pumps; D010835:Phytohemagglutinins; D021122:Protein Subunits; D010042:Ouabain; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D048052:Mitogen-Activated Protein Kinase 3; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium