ArticleAmerican journal of physiology. Renal physiology2015
STE20/SPS1-related proline/alanine-rich kinase (SPAK) is critical for sodium reabsorption in isolated, perfused thick ascending limb.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- AMPK-OXSR1 signaling coordinates proximal tubular sodium transport and is modulated by canagliflozin.Frontiers in endocrinology · 2026Article
- Dysregulation of the WNK4-SPAK/OSR1 pathway has a minor effect on baseline NKCC2 phosphorylation.American journal of physiology. Renal physiology · 2024Article
- Impairment in renal medulla development underlies salt wasting in Clc-k2 channel deficiency.JCI insight · 2021Article
- Intracellular chloride: a regulator of transepithelial transport in the distal nephron.Current opinion in nephrology and hypertension · 2019Review
- WNK4 kinase is a physiological intracellular chloride sensor.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Fructose acutely stimulates NKCC2 activity in rat thick ascending limbs by increasing surface NKCC2 expression.American journal of physiology. Renal physiology · 2019Article
- Sodium and magnesium in the distal convoluted tubule: no longer a couple?Physiological reports · 2018Article
- Renal sodium and magnesium reabsorption are not coupled in a mouse model of Gordon syndrome.Physiological reports · 2018Article
- Suppression of microRNA Activity in Kidney Collecting Ducts Induces Partial Loss of Epithelial Phenotype and Renal Fibrosis.Journal of the American Society of Nephrology : JASN · 2018Article
- Article
- Emerging Targets of Diuretic Therapy.Clinical pharmacology and therapeutics · 2017Review
- Pharmacological targeting of SPAK kinase in disorders of impaired epithelial transport.Expert opinion on therapeutic targets · 2017Review
- WNK signalling pathways in blood pressure regulation.Cellular and molecular life sciences : CMLS · 2017Review
- WNK Kinases in Development and Disease.Current topics in developmental biology · 2017Review
- New insights into sodium transport regulation in the distal nephron: Role of G-protein coupled receptors.World journal of biological chemistry · 2016Review
- Calcineurin and Sorting-Related Receptor with A-Type Repeats Interact to Regulate the Renal Na⁺-K⁺-2Cl⁻ Cotransporter.Journal of the American Society of Nephrology : JASN · 2016Article
- Use of the Ramsay Assay to Measure Fluid Secretion and Ion Flux Rates in the Drosophila melanogaster Malpighian Tubule.Journal of visualized experiments : JoVE · 2015Article
- A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter.Pflugers Archiv : European journal of physiology · 2015Review
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4 authors at 3 institutions in 2 countries.
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Abstract
SPAK [STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase] kinase consists of a full-length (FL-) and an alternatively spliced kidney-specific (KS-) isoform. SPAK regulates the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). The relative abundance and role of FL- vs. KS-SPAK in regulating Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) in thick ascending limb (TAL) are not completely understood. Here, we report that FL-SPAK mRNA was the most abundant in medullary TAL (mTAL), followed by cortical TAL (cTAL) and DCT. KS-SPAK mRNA abundance was relatively lower than FL-SPAK. The ratios of FL-SPAK to KS-SPAK in mTAL, cTAL, and DCT were 12.3, 12.5, and 10.2, respectively. To examine the role of SPAK in the regulation of sodium transport in TAL, we used in vitro microperfusion of mTAL and cTAL isolated from wild-type (WT) and SPAK knockout mice (SPAK-KO) that lack both FL- and KS-SPAK. The rates of sodium absorption in cTAL and mTAL of SPAK-KO mice were 34.5 and 12.5% of WT tubules, respectively. The mRNA levels of related OSR1 kinase and SPAK protease Dnpep in SPAK-KO tubules were not significantly different from WT tubules. We next examined the role of SPAK in the regulation of sodium reabsorption by vasopressin in TAL. Vasopressin increased sodium reabsorption by ∼80% in both mTAL and cTAL from WT mice. While baseline sodium reabsorption was lower in SPAK-KO tubules, vasopressin increased sodium reabsorption over twofold. In conclusion, the combined net effect of SPAK isoforms on sodium reabsorption in TAL is stimulatory. SPAK is not essential for vasopressin stimulation of sodium reabsorption in TAL.
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