+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Expression of rat Na-K-ATPase α2 enables ion pumping but not ouabain-induced signaling in α1-deficient porcine renal epithelial cells



Expression of rat Na-K-ATPase α2 enables ion pumping but not ouabain-induced signaling in α1-deficient porcine renal epithelial cells



American Journal of Physiology. Cell Physiology 309(6): C373



Na-K-ATPase is a fundamental component of ion transport. Four α isoforms of the Na-K-ATPase catalytic α subunit are expressed in human cells. The ubiquitous Na-K-ATPase α1 was recently discovered to also mediate signal transduction through Src kinase. In contrast, α2 expression is limited to a few cell types including myocytes, where it is coupled to the Na(+)/Ca(2+) exchanger. To test whether rat Na-K-ATPase α2 is capable of cellular signaling like its α1 counterpart in a recipient mammalian system, we used an α1 knockdown pig renal epithelial cell (PY-17) to create an α2-expressing cell line with no detectable level of α1 expression. These cells exhibited normal ouabain-sensitive ATPase, but failed to effectively regulate Src. In contrast to α1-expressing cells, ouabain did not stimulate Src kinase or downstream effectors such as ERK and Akt in α2 cells, although their signaling apparatus was intact as evidenced by EGF-mediated signal transduction. Additionally, α2 cells were unable to rescue caveolin-1. Unlike the NaKtide sequence derived from Na-K-ATPase α1, which downregulates basal Src activity, the corresponding α2 NaKtide was unable to inhibit Src in vitro. Finally, coimmunoprecipitation of cellular Src was diminished in α2 cells. These findings indicate that Na-K-ATPase α2 does not regulate Src and, therefore, may not serve the same role in signal transduction as α1. This further implies that the signaling mechanism of Na-K-ATPase is isoform specific, thereby supporting a model where α1 and α2 isoforms play distinct roles in mediating contraction and signaling in myocytes.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 057845085

Download citation: RISBibTeXText

PMID: 26108663

DOI: 10.1152/ajpcell.00103.2015


Related references

I/i-independent death of ouabain-treated renal epithelial cells is not mediated by Na+,K+-ATPase internalization and de novo gene expression. Pfluegers Archiv European Journal of Physiology 455(4): 711-719, 2008

Na+(i)/K+(i)-independent death of ouabain-treated renal epithelial cells is not mediated by Na+,K+-ATPase internalization and de novo gene expression. 2008

Na+]i/[K+]i -independent death of ouabain-treated renal epithelial cells is not mediated by Na+,K+ -ATPase internalization and de novo gene expression. Pflugers Archiv 455(4): 711-719, 2008

Effect of chronic ouabain exposure on Na,K-ATPase regulation in renal epithelial cells. Journal of the American Society of Nephrology 14(Abstracts Issue): 776A, 2003

Na/K-ATPase endocytosis couples pumping and leaking activities in renal epithelial cells: a hypothesis. Cellular and Molecular Biology 52(8): 97-104, 2006

Death of ouabain-treated renal epithelial cells: evidence for p38 MAPK-mediated Na (i) (+) /K (i) (+) -independent signaling. Apoptosis 14(11): 1266-1273, 2009

Cardiotonic steroid-resistant alpha1-Na+,K+-ATPase rescues renal epithelial cells from the cytotoxic action of ouabain: evidence for a Nai+,Ki+ -independent mechanism. Apoptosis 15(1): 55-62, 2010

The expression of suppressor of cytokine signaling-1/3 in renal tubular epithelial cells induced by high glucose. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 22(12): 754-757, 2010

A third mode of ouabain signaling. Focus on "Regulation of ERK1/2 by ouabain and Na-K-ATPase-dependent energy utilization and AMPK activation in parotid acinar cells". American Journal of Physiology. Cell Physiology 295(3): C588, 2008

Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells. Free Radical Research 49(9): 1095-1113, 2015

HMGB1 Enhances the AGE-Induced Expression of CTGF and TGF-β via RAGE-Dependent Signaling in Renal Tubular Epithelial Cells. American Journal of Nephrology 41(3): 257-266, 2015

Na+/K+-ATPase α1 isoform mediates ouabain-induced expression of cyclin D1 and proliferation of rat sertoli cells. Reproduction 144(6): 737-745, 2012

Ouabain is a potent promoter of growth and activator of ERK1/2 in ouabain-resistant rat renal epithelial cells. Journal of Biological Chemistry 278(30): 28160, 2003

Na+/K+-ATPase alpha1 isoform mediates ouabain-induced expression of cyclin D1 and proliferation of rat Sertoli cells. 2013

Cross-talk between phosphatidylinositol 3-kinase signaling cascade and vacuolary H+-ATPase in renal tubular epithelial cells. Molecular Biology of the Cell 13(Suppl.): 429a, 2002