title: Long-term regulation of Na,K-ATPase pump during T-cell proliferation.
abstract: 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 G(0)/G(1)/S transit are associated with the increased number of Na,K-ATPase pumps expressed at the cell surface (as determined by the [(3)H]ouabain binding). Analysis of total RNA (reverse transcription-polymerase chain reaction) and protein (Western blotting) showed a threefold increase in the level of Na,K-ATPase alpha1-subunit and beta1-subunit mRNAs and significant increase in the Na,K-ATPase alpha1-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 signaling via the IL-2 receptor is necessary for the cell cycle-associated upregulation of Na,K-ATPase.
authors.affiliation: Department of Intracellular Signaling and Transport, Institute of Cytology of Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: Inna
authors.initials: I
authors.lastname: Karitskaya
authors.forename: Nikolay
authors.initials: N
authors.lastname: Aksenov
authors.forename: Irina
authors.initials: I
authors.lastname: Vassilieva
authors.forename: Valerii
authors.initials: V
authors.lastname: Zenin
authors.forename: Irina
authors.initials: I
authors.lastname: Marakhova
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D000254:Sodium-Potassium-Exchanging ATPase
references.citation: Biochim Biophys Acta. 1998 Jan 5;1368(1):61-72
references.pmid: 9459585
references.citation: J Exp Biol. 1986 Sep;124:359-73
references.pmid: 2428906
references.citation: Cytokine Growth Factor Rev. 1997 Dec;8(4):313-32
references.pmid: 9620644
references.citation: Science. 1986 Oct 10;234(4773):161-6
references.pmid: 3018928
references.citation: Clin Cancer Res. 1999 Jun;5(6):1569-82
references.pmid: 10389946
references.citation: Int J Hematol. 2001 Apr;73(3):271-7
references.pmid: 11345192
references.citation: Am J Physiol Cell Physiol. 2000 Sep;279(3):C541-66
references.pmid: 10942705
references.citation: Cell. 1999 Mar 5;96(5):611-4
references.pmid: 10089876
references.citation: Biochem Cell Biol. 1987 Feb;65(2):95-104
references.pmid: 3030372
references.citation: Eur J Biochem. 2002 May;269(10):2424-33
references.pmid: 12027879
references.citation: Gen Physiol Biophys. 1989 Jun;8(3):273-82
references.pmid: 2548916
references.citation: J Cell Physiol. 1988 Nov;137(2):329-36
references.pmid: 3263971
references.citation: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references.pmid: 12184808
references.citation: Annu Rev Physiol. 1978;40:19-41
references.pmid: 147644
references.citation: FEBS Lett. 2005 May 23;579(13):2773-80
references.pmid: 15907480
references.citation: Immunobiology. 1986 Jul;171(4-5):436-50
references.pmid: 3091487
references.citation: Cell Physiol Biochem. 2001;11(1):19-26
references.pmid: 11275679
references.citation: FEBS Lett. 1999 Aug 6;456(2):285-9
references.pmid: 10456325
references.citation: Immunity. 1999 Aug;11(2):225-30
references.pmid: 10485657
references.citation: Annu Rev Immunol. 1997;15:707-47
references.pmid: 9143705
references.citation: J Cell Biol. 2000 Sep 18;150(6):1435-44
references.pmid: 10995447
references.citation: Proc Natl Acad Sci U S A. 1997 May 27;94(11):5943-8
references.pmid: 9159180
references.citation: J Immunol. 1999 Apr 1;162(7):3897-904
references.pmid: 10201908
references.citation: Crit Rev Immunol. 1997;17(2):155-78
references.pmid: 9094451
references.citation: J Cell Biol. 1992 Mar;116(5):1071-80
references.pmid: 1740466
references.citation: J Physiol. 1972 Jul;224(2):441-62
references.pmid: 4262774
references.citation: J Cell Physiol. 1995 Nov;165(2):246-53
references.pmid: 7593202
references.citation: Physiol Rev. 1989 Apr;69(2):417-81
references.pmid: 2648419
references.citation: J Biol Chem. 2000 Jan 21;275(3):1976-86
references.pmid: 10636900
references.citation: FEBS Lett. 1986 Oct 6;206(2):199-202
references.pmid: 3019770
references.citation: Soc Gen Physiol Ser. 1985;39:193-204
references.pmid: 2984780
references.citation: J Biol Chem. 2000 Nov 24;275(47):37137-49
references.pmid: 10961988
references.citation: FEBS Lett. 1991 Sep 2;289(1):8-10
references.pmid: 1654277
references.citation: Arch Biochem Biophys. 1987 Feb 1;252(2):515-25
references.pmid: 3028270
references.citation: Annu Rev Physiol. 2002;64:1-18
references.pmid: 11826261
references.citation: Anal Biochem. 1987 Apr;162(1):156-9
references.pmid: 2440339