ArticleAmerican journal of physiology. Renal physiology2015
SPAK-mediated NCC regulation in response to low-K+ diet.
Article in American journal of physiology. Renal physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 58 citations in OpenAlex.
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- Thick Ascending Limb Specific Inactivation of Myh9 and Myh10 Myosin Motors Results in Progressive Kidney Disease and Drives Sex-specific Cellular Adaptation in the Distal Nephron and Collecting Duct.Function (Oxford, England) · 2025Article
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Potassium-Switch Signaling Pathway Dictates Acute Blood Pressure Response to Dietary Potassium.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Kinase Scaffold Cab39 Is Necessary for Phospho-Activation of the Thiazide-Sensitive NCC.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure.The Journal of clinical investigation · 2023Article
- Directing two-way traffic in the kidney: A tale of two ions.The Journal of general physiology · 2022Article
- Sex difference in kidney electrolyte transport III: Impact of low K intake on thiazide-sensitive cation excretion in male and female mice.Pflugers Archiv : European journal of physiology · 2021Article
- WNKs are potassium-sensitive kinases.American journal of physiology. Cell physiology · 2021Article
- Urinary Extracellular Vesicles for Renal Tubular Transporters Expression in Patients With Gitelman Syndrome.Frontiers in medicine · 2021Article
- Low Salt Delivery Triggers Autocrine Release of Prostaglandin E2 From the Aldosterone-Sensitive Distal Nephron in Familial Hyperkalemic Hypertension Mice.Frontiers in physiology · 2021Article
- Dietary potassium and the kidney: lifesaving physiology.Clinical kidney journal · 2020Review
- The WNK signaling pathway and salt-sensitive hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Review
- NBCe1-A is required for the renal ammonia and KAmerican journal of physiology. Renal physiology · 2020Article
- Identification and characterization of alternative STK39 transcripts within human and mouse kidneys reveals species-specific regulation of blood pressure.Physiological reports · 2020Article
- WNK bodies cluster WNK4 and SPAK/OSR1 to promote NCC activation in hypokalemia.American journal of physiology. Renal physiology · 2020Article
- Stimulatory Role of SPAK Signaling in the Regulation of Large Conductance CaFrontiers in physiology · 2020Article
- MgAmerican journal of physiology. Renal physiology · 2019Article
- Clinical importance of potassium intake and molecular mechanism of potassium regulation.Clinical and experimental nephrology · 2019Review
- The interplay of renal potassium and sodium handling in blood pressure regulation: critical role of the WNK-SPAK-NCC pathway.Journal of human hypertension · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The NaCl cotransporter (NCC) of the renal distal convoluted tubule is stimulated by low-K(+) diet by an unknown mechanism. Since recent work has shown that the STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) can function to stimulate NCC by phosphorylation of specific N-terminal sites, we investigated whether the NCC response to low-K(+) diet is mediated by SPAK. Using phospho-specific antibodies in Western blot and immunolocalization studies of wild-type and SPAK knockout (SPAK(-/-)) mice fed a low-K(+) or control diet for 4 days, we found that low-K(+) diet strongly increased total NCC expression and phosphorylation of NCC. This was associated with an increase in total SPAK expression in cortical homogenates and an increase in phosphorylation of SPAK at the S383 activation site. The increased pNCC in response to low-K(+) diet was blunted but not completely inhibited in SPAK(-/-) mice. These findings reveal that SPAK is an important mediator of the increased NCC activation by phosphorylation that occurs in the distal convoluted tubule in response to a low-K(+) diet, but other low-potassium-activated kinases are likely to be involved.
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