ArticleAmerican journal of physiology. Renal physiology2010
RasGRP1 stimulation enhances ubiquitination and endocytosis of the sodium-chloride cotransporter.
Article in American journal of physiology. Renal physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- Association of RASGRP1 polymorphism with vascular complications in Chinese diabetic patients with glycemic control and antihypertensive treatment.Cardiovascular diabetology · 2024Article
- KDM6A Demethylase Regulates Renal Sodium Excretion and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Kelch-like protein 3 in human disease and therapy.Molecular biology reports · 2022Review
- COP9 signalosome deletion promotes renal injury and distal convoluted tubule remodeling.American journal of physiology. Renal physiology · 2022Article
- SIRT7 modulates the stability and activity of the renal K-Cl cotransporter KCC4 through deacetylation.EMBO reports · 2021Article
- Regulatory control of the Na-Cl co-transporter NCC and its therapeutic potential for hypertension.Acta pharmaceutica Sinica. B · 2021Review
- 14-3-3γ, a novel regulator of the large-conductance CaAmerican journal of physiology. Renal physiology · 2020Article
- ERK1,2 Signalling Pathway along the Nephron and Its Role in Acid-base and Electrolytes Balance.International journal of molecular sciences · 2019Review
- Role of the alternative splice variant of NCC in blood pressure control.Channels (Austin, Tex.) · 2018Review
- The thiazide sensitive sodium chloride co-transporter NCC is modulated by site-specific ubiquitylation.Scientific reports · 2017Article
- Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway.Scientific reports · 2016Article
- Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway.American journal of physiology. Renal physiology · 2015Article
- Revisiting the NaCl cotransporter regulation by with-no-lysine kinases.American journal of physiology. Cell physiology · 2015Review
- WNK1 activates large-conductance Ca2+-activated K+ channels through modulation of ERK1/2 signaling.Journal of the American Society of Nephrology : JASN · 2015Article
- Article
- FGF23 regulates renal sodium handling and blood pressure.EMBO molecular medicine · 2014Article
- Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter NCC and subsequent clathrin-mediated endocytosis.The Journal of biological chemistry · 2014Article
- The sodium chloride cotransporter SLC12A3: new roles in sodium, potassium, and blood pressure regulation.Pflugers Archiv : European journal of physiology · 2014Review
- WNK4 inhibition of ENaC is independent of Nedd4-2-mediated ENaC ubiquitination.American journal of physiology. Renal physiology · 2013Article
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6 authors at 2 institutions in 2 countries.
Funding
Abstract
The sodium-chloride cotransporter (NCC) is the principal salt-absorptive pathway in the distal convoluted tubule. Recently, we described a novel pathway of NCC regulation in which phorbol esters (PE) stimulate Ras guanyl-releasing protein 1 (RasGRP1), triggering a cascade ultimately activating ERK1/2 MAPK and decreasing NCC cell surface expression (Ko B, Joshi LM, Cooke LL, Vazquez N, Musch MW, Hebert SC, Gamba G, Hoover RS. Proc Natl Acad Sci USA 104: 20120-20125, 2007). Little is known about the mechanisms which underlie these effects on NCC activity. Regulation of NCC via changes in NCC surface expression has been reported, but endocytosis of NCC has not been demonstrated. In this study, utilizing biotinylation, internalization assays, and a dynamin dominant-negative construct, we demonstrate that the regulation of NCC by PE occurs via an enhancement in internalization of NCC and is dynamin dependent. In addition, immunoprecipitation of NCC and subsequent immunoblotting for ubiquitin showed increased ubiquitination of NCC with phorbol ester treatment. MEK1/2 inhibitors and gene silencing of RasGRP1 indicated that this effect was dependent on RasGRP1 and ERK1/2 activation. Inhibition of ubiquitination prevents any PE-mediated decrease in NCC surface expression as measured by biotinylation or NCC activity as measured by radiotracer uptake. These findings confirmed that the PE effect on NCC is mediated by endocytosis of NCC. Furthermore, ubiquitination of NCC is essential for this process and this ubiquitination is dependent upon RasGRP1-mediated ERK1/2 activation.
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