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Cell and Tissue Biology

, 2:23 | Cite as

Long-term regulation of Na+/K+-ATPase pump in human lymphocytes: Role of JAK/STAT and MAPK signaling pathways

  • I. A. Karitskaya
  • N. D. Aksenov
  • I. O. Vasileva
  • E. G. Strelkova
  • I. I. Marakhova
Article
  • 52 Downloads

Abstract

In interleukin-2 (IL-2)-stimulated human lymphocytes, a study has been carried out on the transport activity of an Na+/K+-ATPase pump (assessed by ouabain-sensitive Rb+ influx), the expression of the Na+/K+-ATPase at the protein level (determined by immunoblotting), and mRNA (the RT-PCR method), as well as the phosphorylation levels of STAT5 and STAT3 transcription factors and ERK1/2 tyrosine kinase. In competent lymphocytes, IL-2 has been found to increase the total amount of Na+/K+-ATPase α1mRNA and β1mRNA by a factor of 3.5–4 for 24 h. During the inhibition of the IL-2-induced ERK1/2 activity in the presence of MAP-kinase inhibitor PD98059, a rise in the rubidium influx is absent, while the increment of the α1 protein of Na+/K+-ATPase decreases. None of the tested kinase inhibitors affected the intracellular content of monovalent cations in resting and IL-2-stimulated lymphocytes. Inhibitors of JAK3 tyrosine kinase (B-42, WHI-P131) have been shown to decrease the IL-2-induced increase of the STAT5 and STAT3 phosphorylated forms and, at the same time, to inhibit the rise of a rubidium influx into the cell that is characteristic of the proliferative response prereplicative stage, as well as to increase the expression of the catalytical Na+/K+-ATPase α1-subunit. The inhibition of the protein kinases ERK1/2 by PD98059 (20 μM) suppressed the long-term increase both in the rubidium influx and in the α1-subunit accumulation. It is concluded that the long-term increase of the sodium pump transport activity, which is associated with the IL-2-dependent stage of proliferative response and is based on synthesis of new Na+/K+-ATPase subunits, is controlled through the JAK/STAT and ERK1/2-MAP-kinase pathways of intracellular signaling.

Key words

Na+/K+pump Na+/K+-ATPase tyrosine kinase JAK3 transcription factors STAT5 and STAT3 tyrosine kinase ERK1/2 interleukin-2 proliferative response human lymphocytes 

Abbreviations

IL-2

interleukin-2

PHA

phytoheagglutinin

ERK1/2

extracellular signal-regulated kinase 1 and 2

JAK

Janus kinase

MAP-kinase

mitogen-activated protein kinase

STAT

signal transducers and activators of transcription

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Copyright information

© MAIK Nauka 2008

Authors and Affiliations

  • I. A. Karitskaya
    • 1
  • N. D. Aksenov
    • 1
  • I. O. Vasileva
    • 1
  • E. G. Strelkova
    • 1
  • I. I. Marakhova
    • 1
  1. 1.Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia

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