ArticleThe Journal of general physiology2007
Acute downregulation of ENaC by EGF involves the PY motif and putative ERK phosphorylation site.
Article in The Journal of general physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- Ureaplasma-driven inhibition of the epithelial Na+ transport in fetal alveolar cells: A novel mechanism of Ureaplasma-mediated preterm lung disease.PLoS pathogens · 2025Article
- Phosphoproteomic response to epidermal growth factor in native rat inner medullary collecting duct.American journal of physiology. Renal physiology · 2025Article
- KDM6A Demethylase Regulates Renal Sodium Excretion and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Epidermal growth factor strongly affects epithelial NaScientific reports · 2021Article
- Paracrine stimulation of perinatal lung functional and structural maturation by mesenchymal stem cells.Stem cell research & therapy · 2020Article
- ERK1,2 Signalling Pathway along the Nephron and Its Role in Acid-base and Electrolytes Balance.International journal of molecular sciences · 2019Review
- Arachidonic acid monooxygenase: Genetic and biochemical approaches to physiological/pathophysiological relevance.Prostaglandins & other lipid mediators · 2015Review
- Cigarette smoke exposure reveals a novel role for the MEK/ERK1/2 MAPK pathway in regulation of CFTR.Biochimica et biophysica acta · 2015Article
- H-Ras mediates the inhibitory effect of epidermal growth factor on the epithelial Na+ channel.PloS one · 2015Article
- Role of Rho GDP dissociation inhibitor α in control of epithelial sodium channel (ENaC)-mediated sodium reabsorption.The Journal of biological chemistry · 2014Article
- Nerve growth factor reduces amiloride-sensitive Na+ transport in human airway epithelial cells.Physiological reports · 2014Article
- The Cyp2c44 epoxygenase regulates epithelial sodium channel activity and the blood pressure responses to increased dietary salt.The Journal of biological chemistry · 2014Article
- Epidermal growth factors in the kidney and relationship to hypertension.American journal of physiology. Renal physiology · 2013Review
- Epoxyeicosatrienoic acids (EETs) regulate epithelial sodium channel activity by extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated phosphorylation.The Journal of biological chemistry · 2013Article
- Glioma-specific cation conductance regulates migration and cell cycle progression.The Journal of biological chemistry · 2012Article
- Regulation and dysregulation of epithelial Na+ channels.Clinical and experimental nephrology · 2012Review
- Epidermal growth factor-mediated proliferation and sodium transport in normal and PKD epithelial cells.Biochimica et biophysica acta · 2011Review
- Physiology of endothelin and the kidney.Comprehensive Physiology · 2011Review
- Regulation of blood pressure and salt homeostasis by endothelin.Physiological reviews · 2011Review
- Regulation of sodium transport by ENaC in the kidney.Current opinion in nephrology and hypertension · 2010Review
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
The epithelial sodium channel (ENaC) is expressed in a variety of tissues, including the renal collecting duct, where it constitutes the rate-limiting step for sodium reabsorption. Liddle's syndrome is caused by gain-of-function mutations in the beta and gamma subunits of ENaC, resulting in enhanced Na reabsorption and hypertension. Epidermal growth factor (EGF) causes acute inhibition of Na absorption in collecting duct principal cells via an extracellular signal-regulated kinase (ERK)-dependent mechanism. In experiments with primary cultures of collecting duct cells derived from a mouse model of Liddle's disease (beta-ENaC truncation), it was found that EGF inhibited short-circuit current (Isc) by 24 +/- 5% in wild-type cells but only by 6 +/- 3% in homozygous mutant cells. In order to elucidate the role of specific regions of the beta-ENaC C terminus, Madin-Darby canine kidney (MDCK) cell lines that express beta-ENaC with mutation of the PY motif (P616L), the ERK phosphorylation site (T613A), and C terminus truncation (R564stop) were created using the Phoenix retroviral system. All three mutants exhibited significant attenuation of the EGF-induced inhibition of sodium current. In MDCK cells with wild-type beta-ENaC, EGF-induced inhibition of Isc (<30 min) was fully reversed by exposure to an ERK kinase inhibitor and occurred with no change in ENaC surface expression, indicative of an effect on channel open probability (P(o)). At later times (>30 min), EGF-induced inhibition of Isc was not reversed by an ERK kinase inhibitor and was accompanied by a decrease in ENaC surface expression. Our results are consistent with an ERK-mediated decrease in ENaC open probability and enhanced retrieval of sodium channels from the apical membrane.
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