ArticleJournal of the American Society of Nephrology : JASN2011
Nedd4-2 modulates renal Na+-Cl- cotransporter via the aldosterone-SGK1-Nedd4-2 pathway.
Article in Journal of the American Society of Nephrology : JASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
91 citing papers in PubMed, 163 citations in OpenAlex.
- No lysine? No problem: the surprising roles of WNK kinases in physiology and disease.The Biochemical journal · 2026Review
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- Tubular epithelial cells promote macrophage pyroptosis through PANX1-extracellular ATP-P2X7 signaling in aldosterone-dependent renal injury.Cell death & disease · 2026Article
- Impact of aldosterone deficiency on the development of diuretic resistance in mice.Pflugers Archiv : European journal of physiology · 2025Article
- Exploring the Common Pathogenic Mechanisms of Psoriasis and Atopic Dermatitis: The Interaction between SGK1 and TIGIT Signaling Pathways.Inflammation · 2025Article
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Primary Role of the Kidney in Pathogenesis of Hypertension.Life (Basel, Switzerland) · 2024Review
- Dietary NaCellular and molecular life sciences : CMLS · 2023Article
- Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Control of sodium and potassium homeostasis by renal distal convoluted tubules.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- In Primary Aldosteronism Acute Potassium Chloride Supplementation Suppresses Abundance and Phosphorylation of the Sodium-Chloride Cotransporter.Kidney360 · 2022Article
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway.International journal of molecular sciences · 2022Article
- Article
- Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains.Biophysical journal · 2022Article
- Acetylation, Phosphorylation, Ubiquitination (Oh My!): Following Post-Translational Modifications on the Ubiquitin Road.Biomolecules · 2022Review
- Review
- Does the early aldosterone-induced SGK1 play a role in early Kaliuresis?Physiological reports · 2022Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
Regulation of renal Na(+) transport is essential for controlling blood pressure, as well as Na(+) and K(+) homeostasis. Aldosterone stimulates Na(+) reabsorption by the Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule (DCT) and by the epithelial Na(+) channel (ENaC) in the late DCT, connecting tubule, and collecting duct. Aldosterone increases ENaC expression by inhibiting the channel's ubiquitylation and degradation; aldosterone promotes serum-glucocorticoid-regulated kinase SGK1-mediated phosphorylation of the ubiquitin-protein ligase Nedd4-2 on serine 328, which prevents the Nedd4-2/ENaC interaction. It is important to note that aldosterone increases NCC protein expression by an unknown post-translational mechanism. Here, we present evidence that Nedd4-2 coimmunoprecipitated with NCC and stimulated NCC ubiquitylation at the surface of transfected HEK293 cells. In Xenopus laevis oocytes, coexpression of NCC with wild-type Nedd4-2, but not its catalytically inactive mutant, strongly decreased NCC activity and surface expression. SGK1 prevented this inhibition in a kinase-dependent manner. Furthermore, deficiency of Nedd4-2 in the renal tubules of mice and in cultured mDCT(15) cells upregulated NCC. In contrast to ENaC, Nedd4-2-mediated inhibition of NCC did not require the PY-like motif of NCC. Moreover, the mutation of Nedd4-2 at either serine 328 or 222 did not affect SGK1 action, and mutation at both sites enhanced Nedd4-2 activity and abolished SGK1-dependent inhibition. Taken together, these results suggest that aldosterone modulates NCC protein expression via a pathway involving SGK1 and Nedd4-2 and provides an explanation for the well-known aldosterone-induced increase in NCC protein expression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.