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

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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.

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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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Authors and Affiliations

  1. Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia

    I. A. Karitskaya, N. D. Aksenov, I. O. Vasileva, E. G. Strelkova & I. I. Marakhova

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  1. I. A. Karitskaya
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  2. N. D. Aksenov
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  3. I. O. Vasileva
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  4. E. G. Strelkova
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  5. I. I. Marakhova
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Correspondence to I. I. Marakhova.

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Original Russian Text © I.A. Karitskaya, N.D. Aksenov, I.O. Vasileva, E.G. Strelkova, I.I. Marakhova, 2008, published in Tsitologiya, Vol. 50, No. 1, 2008.

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Karitskaya, I.A., Aksenov, N.D., Vasileva, I.O. et al. Long-term regulation of Na+/K+-ATPase pump in human lymphocytes: Role of JAK/STAT and MAPK signaling pathways. Cell Tiss. Biol. 2, 23–32 (2008). https://doi.org/10.1134/S1990519X08010045

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  • DOI: https://doi.org/10.1134/S1990519X08010045

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