DOI: 10.1046/j.1432-1033.2002.02910.x. Na<sup>+</sup>/K<sup>+</sup>‐ATPase as a signal transducer

10.1046/j.1432-1033.2002.02910.x

Crossref journal-article

Wiley

European Journal of Biochemistry (311)

Abstract

Na+/K+‐ATPase as an energy transducing ion pump has been studied extensively since its discovery in 1957. Although early findings suggested a role for Na+/K+‐ATPase in regulation of cell growth and expression of various genes, only in recent years the mechanisms through which this plasma membrane enzyme communicates with the nucleus have been studied. This research, carried out mostly on cardiac myocytes, shows that in addition to pumping ions, Na+/K+‐ATPase interacts with neighboring membrane proteins and organized cytosolic cascades of signaling proteins to send messages to the intracellular organelles. The signaling pathways that are rapidly elicited by the interaction of ouabain with Na+/K+‐ATPase, and are independent of changes in intracellular Na+ and K+ concentrations, include activation of Src kinase, transactivation of the epidermal growth factor receptor by Src, activation of Ras and p42/44 mitogen‐activated protein kinases, and increased generation of reactive oxygen species by mitochondria. In cardiac myocytes, the resulting downstream events include the induction of some early response proto‐oncogenes, activation of the transcription factors, activator protein‐1 and nuclear factor kappa‐B, regulation of a number of cardiac growth‐related genes, and stimulation of protein synthesis and myocyte hypertrophy. For these downstream events, the induced reactive oxygen species and rise in intracellular Ca2+ are essential second messengers. In cells other than cardiac myocytes, the proximal pathways linked to Na+/K+‐ATPase through protein–protein interactions are similar to those reported in myocytes, but the downstream events and consequences may be significantly different. The likely extracellular physiological stimuli for the signal transducing function of Na+/K+‐ATPase are the endogenous ouabain‐like hormones, and changes in extracellular K+ concentration.

Bibliography

Xie, Z., & Askari, A. (2002). Na+/K+âATPase as a signal transducer. European Journal of Biochemistry, 269(10), 2434â2439. Portico.

Authors 2

Zijian Xie (first)
Amir Askari (additional)

References 40 Referenced 489

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10.1172/JCI116781
10.1046/j.1471-4159.1997.69052189.x
10.1007/BF00233355
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{'key': 'e_1_2_10_15_2', 'first-page': '1559', 'article-title': 'Na+,K+‐ATPase inhibitors down‐regulate gene expression of the intracellular signaling protein 14‐3‐3 in rat lens', 'volume': '289', 'author': 'McGowan M.H.', 'year': '1999', 'journal-title': 'J. Pharmacol. Exp. Ther.'} / J. Pharmacol. Exp. Ther. / Na+,K+‐ATPase inhibitors down‐regulate gene expression of the intracellular signaling protein 14‐3‐3 in rat lens by McGowan M.H. (1999)
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10.1046/j.1432-1033.2002.02911.x

Dates

Type	When
Created	22 years, 5 months ago (March 11, 2003, 1:30 p.m.)
Deposited	1 year, 10 months ago (Oct. 30, 2023, 10:34 p.m.)
Indexed	4 hours, 29 minutes ago (Sept. 6, 2025, 3:22 p.m.)
Issued	23 years, 3 months ago (May 7, 2002)
Published	23 years, 3 months ago (May 7, 2002)
Published Online	23 years, 3 months ago (May 7, 2002)
Published Print	23 years, 3 months ago (May 15, 2002)

Funders 0

None

BibTeX

@article{Xie_2002, title={Na+/K+‐ATPase as a signal transducer}, volume={269}, ISSN={1432-1033}, url={http://dx.doi.org/10.1046/j.1432-1033.2002.02910.x}, DOI={10.1046/j.1432-1033.2002.02910.x}, number={10}, journal={European Journal of Biochemistry}, publisher={Wiley}, author={Xie, Zijian and Askari, Amir}, year={2002}, month=may, pages={2434–2439} }

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