Regulation of Na+/H+ exchanger gene expression: mitogenic stimulation increases NHE1 promoter activity

The American Journal of Physiology
P BessonL Fliegel

Abstract

We examined factors important in regulation of expression of the Na+/H+ exchanger gene in NIH/3T3 cells. A stable fibroblast cell line was generated that contained a 1.1-kb proximal fragment of the mouse NHE1 promoter. The addition of serum to serum-starved cells resulted in an increase in activity of the NHE1 promoter. The mitogenic agonists insulin, thrombin, and epidermal growth factor also increased transcription from the NHE1 promoter. Phorbol esters also increased NHE1 promoter-directed transcription, whereas the serine/threonine protein kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine inhibited this stimulation. The protein kinase inhibitors GF-109203X, PD-98059, and genistein all stimulated promoter activity. Promoter deletion analysis and gel mobility shift assays showed that a region between 0.9 and 1.1 kb from the start site was involved in mediating the effect of mitogenic stimulation. The results show that a variety of mitogenic factors can activate the NHE1 promoter during cell growth and proliferation.

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Citations

Nov 28, 2000·Cell Motility and the Cytoskeleton·B W BernsteinJ R Bamburg
Mar 20, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·J E MelvinW Scott
Nov 21, 2002·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Emily Slepkov, Larry Fliegel
Nov 28, 2002·American Journal of Physiology. Renal Physiology·Karen L WuJeffrey R Schelling
Jun 14, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Carmen V Rieder, Larry Fliegel
Jun 1, 2002·The Journal of Biological Chemistry·Xiuju LiLarry Fliegel
Apr 6, 2006·Pflügers Archiv : European journal of physiology·Stine Falsig Pedersen
Apr 8, 2009·The Journal of Cell Biology·Linda SchneiderStine Falsig Pedersen
Feb 15, 2015·Cellular and Molecular Life Sciences : CMLS·Mark D ParkerJeffrey R Schelling
Oct 22, 2016·Archives of Physiology and Biochemistry·Sandeep SinghSyed Ibrahim Rizvi
Feb 13, 2001·European Journal of Biochemistry·F Fernandez-Rachubinski, L Fliegel
Jun 21, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Eon J RiosLarissa A Shimoda
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