Wnk4

Summary

Gene Symbol: Wnk4
Description: WNK lysine deficient protein kinase 4
Alias: 2010002J11Rik, Pha2b, Prkwnk4, serine/threonine-protein kinase WNK4, protein kinase with no lysine 4, protein kinase, lysine deficient 4
Species: mouse
Products:     Wnk4

Top Publications

  1. Kahle K, Gimenez I, Hassan H, Wilson F, Wong R, Forbush B, et al. WNK4 regulates apical and basolateral Cl- flux in extrarenal epithelia. Proc Natl Acad Sci U S A. 2004;101:2064-9 pubmed
    Mutations in the serine-threonine kinase WNK4 [with no lysine (K) 4] cause pseudohypoaldosteronism type II, a Mendelian disease featuring hypertension with hyperkalemia...
  2. Castañeda Bueno M, Cervantes Pérez L, Vazquez N, Uribe N, Kantesaria S, Morla L, et al. Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process. Proc Natl Acad Sci U S A. 2012;109:7929-34 pubmed publisher
    ..salt-sensitive form of hypertension with hyperkalemia in humans caused by mutations in the with-no-lysine kinase 4 (WNK4). Several studies have shown that WNK4 modulates the activity of the renal Na(+)Cl(-) cotransporter, NCC...
  3. O Reilly M, Marshall E, Macgillivray T, Mittal M, Xue W, Kenyon C, et al. Dietary electrolyte-driven responses in the renal WNK kinase pathway in vivo. J Am Soc Nephrol. 2006;17:2402-13 pubmed
    WNK1 and WNK4 are unusual serine/threonine kinases with atypical positioning of the catalytic active-site lysine (WNK: With-No-K[lysine])...
  4. Golbang A, Cope G, Hamad A, Murthy M, Liu C, Cuthbert A, et al. Regulation of the expression of the Na/Cl cotransporter by WNK4 and WNK1: evidence that accelerated dynamin-dependent endocytosis is not involved. Am J Physiol Renal Physiol. 2006;291:F1369-76 pubmed
    ..no lysine kinases or WNKs), WNK1 and WNK4, are encoded by the disease genes for Gordon syndrome (PRKWNK1 and PRKWNK4), a rare monogenic syndrome of hypertension and hyperkalemia...
  5. Hossain Khan M, Sohara E, Ohta A, Chiga M, Inoue Y, Isobe K, et al. Phosphorylation of Na-Cl cotransporter by OSR1 and SPAK kinases regulates its ubiquitination. Biochem Biophys Res Commun. 2012;425:456-61 pubmed publisher
    ..Thus, we demonstrated that NCC phosphorylation decreased NCC ubiquitination, which may contribute to the increase of NCC abundance mostly on plasma membranes. ..
  6. Isobe K, Mori T, Asano T, Kawaguchi H, Nonoyama S, Kumagai N, et al. Development of enzyme-linked immunosorbent assays for urinary thiazide-sensitive Na-Cl cotransporter measurement. Am J Physiol Renal Physiol. 2013;305:F1374-81 pubmed publisher
    ..Thus we established highly sensitive and quantitative assays for urinary NCC, which could be valuable tools for estimating NCC activity in vivo. ..
  7. Chiga M, Rafiqi F, Alessi D, Sohara E, Ohta A, Rai T, et al. Phenotypes of pseudohypoaldosteronism type II caused by the WNK4 D561A missense mutation are dependent on the WNK-OSR1/SPAK kinase cascade. J Cell Sci. 2011;124:1391-5 pubmed publisher
    We recently reported increased phosphorylation of the NaCl cotransporter (NCC) in Wnk4(D561A/+) knock-in mice, an ideal model of the human hereditary hypertensive disease pseudohypoaldosteronism type II (PHAII)...
  8. Yang C, Zhu X, Ellison D. The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex. J Clin Invest. 2007;117:3403-11 pubmed
    ..FHHt) was shown to result from activation of the thiazide-sensitive Na-Cl cotransporter (NCC) by mutations in WNK4, although the mechanism for this effect remains unknown...
  9. Ahlstrom R, Yu A. Characterization of the kinase activity of a WNK4 protein complex. Am J Physiol Renal Physiol. 2009;297:F685-92 pubmed publisher
    Mutations in WNK4 protein kinase cause pseudohypoaldosteronism type II (PHAII), a genetic disorder that is characterized by renal NaCl and K(+) retention leading to hypertension and hyperkalemia...

More Information

Publications59

  1. Yang S, Morimoto T, Rai T, Chiga M, Sohara E, Ohno M, et al. Molecular pathogenesis of pseudohypoaldosteronism type II: generation and analysis of a Wnk4(D561A/+) knockin mouse model. Cell Metab. 2007;5:331-44 pubmed
    WNK1 and WNK4 mutations have been reported to cause pseudohypoaldosteronism type II (PHAII), an autosomal-dominant disorder characterized by hyperkalemia and hypertension...
  2. Gagnon K, England R, Delpire E. Volume sensitivity of cation-Cl- cotransporters is modulated by the interaction of two kinases: Ste20-related proline-alanine-rich kinase and WNK4. Am J Physiol Cell Physiol. 2006;290:C134-42 pubmed
    ..study, we have demonstrated functional interaction between Ste20-related proline-alanine-rich kinase (SPAK), WNK4 [with no lysine (K)], and the widely expressed Na+-K+-2Cl- cotransporter type 1 (NKCC1)...
  3. Wilson F, Kahle K, Sabath E, Lalioti M, Rapson A, Hoover R, et al. Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4. Proc Natl Acad Sci U S A. 2003;100:680-4 pubmed
    Mutations in the serine-threonine kinases WNK1 and WNK4 [with no lysine (K) at a key catalytic residue] cause pseudohypoaldosteronism type II (PHAII), a Mendelian disease featuring hypertension, hyperkalemia, hyperchloremia, and metabolic ..
  4. Ohno M, Uchida K, Ohashi T, Nitta K, Ohta A, Chiga M, et al. Immunolocalization of WNK4 in mouse kidney. Histochem Cell Biol. 2011;136:25-35 pubmed publisher
    Initial reports claim that WNK4 localization is mainly at intercellular junctions of distal convoluted tubules (DCT) and cortical collecting ducts (CCD) in the kidney...
  5. Yang C, Angell J, Mitchell R, Ellison D. WNK kinases regulate thiazide-sensitive Na-Cl cotransport. J Clin Invest. 2003;111:1039-45 pubmed
    ..Mutations in two members of the WNK kinase family, WNK1 and WNK4, cause the disease...
  6. Chiga M, Rai T, Yang S, Ohta A, Takizawa T, Sasaki S, et al. Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone. Kidney Int. 2008;74:1403-9 pubmed publisher
    Pseudohypoaldosteronism type II (PHAII) is caused by mutations in the WNK1 and WNK4 genes (WNK with-no-lysine kinase)...
  7. Wilson F, Disse Nicodeme S, Choate K, Ishikawa K, Nelson Williams C, Desitter I, et al. Human hypertension caused by mutations in WNK kinases. Science. 2001;293:1107-12 pubmed
    ..Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein...
  8. Ohta A, Rai T, Yui N, Chiga M, Yang S, Lin S, et al. Targeted disruption of the Wnk4 gene decreases phosphorylation of Na-Cl cotransporter, increases Na excretion and lowers blood pressure. Hum Mol Genet. 2009;18:3978-86 pubmed publisher
    We recently generated Wnk4(D561A/+) knockin mice and found that a major pathogenesis of pseudohypoaldosteronism type II was the activation of the OSR1/SPAK kinase-NaCl cotransporter (NCC) phosphorylation cascade by the mutant WNK4...
  9. San Cristobal P, Pacheco Alvarez D, Richardson C, Ring A, Vazquez N, Rafiqi F, et al. Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway. Proc Natl Acad Sci U S A. 2009;106:4384-9 pubmed publisher
    Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and high serum K(+) levels (hyperkalemia)...
  10. Lalioti M, Zhang J, Volkman H, Kahle K, Hoffmann K, Toka H, et al. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nat Genet. 2006;38:1124-32 pubmed
    ..Mutations in the gene encoding the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and hyperkalemia...
  11. Ring A, Leng Q, Rinehart J, Wilson F, Kahle K, Hebert S, et al. An SGK1 site in WNK4 regulates Na+ channel and K+ channel activity and has implications for aldosterone signaling and K+ homeostasis. Proc Natl Acad Sci U S A. 2007;104:4025-9 pubmed
    ..Mutations in WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring increased renal NaCl reabsorption and impaired K(..
  12. Subramanya A, Liu J, Ellison D, Wade J, Welling P. WNK4 diverts the thiazide-sensitive NaCl cotransporter to the lysosome and stimulates AP-3 interaction. J Biol Chem. 2009;284:18471-80 pubmed publisher
    With-no-lysine kinase 4 (WNK4) inhibits electroneutral sodium chloride reabsorption by attenuating the cell surface expression of the thiazide-sensitive NaCl cotransporter (NCC)...
  13. Shibata S, Zhang J, Puthumana J, Stone K, Lifton R. Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. Proc Natl Acad Sci U S A. 2013;110:7838-43 pubmed publisher
    ..By MS and coimmunoprecipitation, we show that KLHL3 normally binds to WNK1 and WNK4, members of WNK (with no lysine) kinase family that have previously been found mutated in PHAII...
  14. Yang S, Hsu Y, Chiga M, Rai T, Sasaki S, Uchida S, et al. Mechanisms for hypercalciuria in pseudohypoaldosteronism type II-causing WNK4 knock-in mice. Endocrinology. 2010;151:1829-36 pubmed publisher
    The mechanisms underlying hypercalciuria in pseudohypoaldosteronism type II (PHAII) caused by WNK4 mutations remain unclear...
  15. Andrukhova O, Smorodchenko A, Egerbacher M, Streicher C, Zeitz U, Goetz R, et al. FGF23 promotes renal calcium reabsorption through the TRPV5 channel. EMBO J. 2014;33:229-46 pubmed publisher
    ..are regulated by FGF23, which binds the FGF receptor-?Klotho complex and activates a signaling cascade involving ERK1/2, SGK1, and WNK4. Our data thereby identify FGF23, not ?Klotho, as a calcium-conserving hormone in the kidney.
  16. Terker A, Zhang C, Erspamer K, Gamba G, Yang C, Ellison D. Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis. Kidney Int. 2016;89:127-34 pubmed publisher
    ..Kinase assay studies showed that chloride inhibits WNK4 kinase activity at lower concentrations than it inhibits activity of WNK1 or WNK3...
  17. Zhang C, Wang L, Su X, Zhang J, Lin D, Wang W. ENaC and ROMK activity are inhibited in the DCT2/CNT of TgWnk4PHAII mice. Am J Physiol Renal Physiol. 2017;312:F682-F688 pubmed publisher
    Mice transgenic for genomic segments harboring PHAII (pseudohypoaldosteronism type II) mutant Wnk4 (with-No-Lysine kinase 4) (TgWnk4PHAII) have hyperkalemia which is currently believed to be the result of high activity of Na-Cl ..
  18. Takahashi D, Mori T, Sohara E, Tanaka M, Chiga M, Inoue Y, et al. WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice. EBioMedicine. 2017;18:118-127 pubmed publisher
    ..In this study, we found that WNK4 was expressed in mouse adipose tissue and 3T3-L1 adipocytes...
  19. Yamauchi K, Yang S, Ohta A, Sohara E, Rai T, Sasaki S, et al. Apical localization of renal K channel was not altered in mutant WNK4 transgenic mice. Biochem Biophys Res Commun. 2005;332:750-5 pubmed
    Missense mutations in the WNK4 gene have been postulated to cause pseudohypoaldosteronism type II, an autosomal-dominant disorder characterized by hyperkalemia and hypertension...
  20. McCormick J, Yang C, Zhang C, Davidge B, Blankenstein K, Terker A, et al. Hyperkalemic hypertension-associated cullin 3 promotes WNK signaling by degrading KLHL3. J Clin Invest. 2014;124:4723-36 pubmed publisher
  21. Mori Y, Mori T, Wakabayashi M, Yoshizaki Y, Zeniya M, Sohara E, et al. Involvement of selective autophagy mediated by p62/SQSTM1 in KLHL3-dependent WNK4 degradation. Biochem J. 2015;472:33-41 pubmed publisher
    We reported that kelch-like protein 3 (KLHL3)-Cullin3 E3 ligase ubiquitinates with-no-lysine kinase 4 (WNK4) and that impaired WNK4 ubiquitination causes pseudohypoaldosteronism type II, a hereditary hypertensive disease...
  22. Melo Z, Cruz Rangel S, Bautista R, Vazquez N, Castañeda Bueno M, Mount D, et al. Molecular evidence for a role for K(+)-Cl(-) cotransporters in the kidney. Am J Physiol Renal Physiol. 2013;305:F1402-11 pubmed publisher
    ..The increased protein expression of KCC4 by a low-salt diet was also observed in WNK4 knockout mice, suggesting that upregulation of KCC4 in these circumstances is not WNK4 dependent...
  23. Kasagi Y, Takahashi D, Aida T, Nishida H, Nomura N, Zeniya M, et al. Impaired degradation of medullary WNK4 in the kidneys of KLHL2 knockout mice. Biochem Biophys Res Commun. 2017;487:368-374 pubmed publisher
    Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, Kelch-like 3 (KLHL3), and Cullin3 (CUL3) genes were identified as being responsible for hereditary hypertensive disease pseudohypoaldosteronism type II (PHAII)...
  24. Salzler H, Griffiths R, Ruiz P, Chi L, Frey C, Marchuk D, et al. Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus. Kidney Int. 2007;72:1226-32 pubmed
    ..Our studies have identified a region spanning approximately 8 cM on mouse chromosome 11 that is associated with susceptibility to hypertension and albuminuria in CKD. ..
  25. Zimdahl H, Kreitler T, Gosele C, Ganten D, Hubner N. Conserved synteny in rat and mouse for a blood pressure QTL on human chromosome 17. Hypertension. 2002;39:1050-2 pubmed
    ..It is of interest that this region also contains Wnk4, a gene previously identified to cause pseudohypoaldosteronism type II and human hypertension...
  26. Mu S, Shimosawa T, Ogura S, Wang H, Uetake Y, Kawakami Mori F, et al. Epigenetic modulation of the renal ?-adrenergic-WNK4 pathway in salt-sensitive hypertension. Nat Med. 2011;17:573-80 pubmed publisher
    ..we found that ?(2)-adrenergic receptor (?(2)AR) stimulation led to decreased transcription of the gene encoding WNK4, a regulator of sodium reabsorption...
  27. Lee B, Min X, Heise C, Xu B, Chen S, Shu H, et al. WNK1 phosphorylates synaptotagmin 2 and modulates its membrane binding. Mol Cell. 2004;15:741-51 pubmed
    WNK (with no lysine [K]) protein kinases were named for their unique active site organization. Mutations in WNK1 and WNK4 cause a familial form of hypertension by undefined mechanisms...
  28. Na T, Wu G, Peng J. Disease-causing mutations in the acidic motif of WNK4 impair the sensitivity of WNK4 kinase to calcium ions. Biochem Biophys Res Commun. 2012;419:293-8 pubmed publisher
    b>WNK4 is a serine/threonine protein kinase that is involved in pseudohypoaldosteronism type II (PHAII), a Mendelian form disorder featuring hypertension and hyperkalemia...
  29. Rinehart J, Vazquez N, Kahle K, Hodson C, Ring A, Gulcicek E, et al. WNK2 kinase is a novel regulator of essential neuronal cation-chloride cotransporters. J Biol Chem. 2011;286:30171-80 pubmed publisher
    ..The kinase(s) that performs this function in the nervous system are not known with certainty. WNK1 and WNK4, members of the WNK (with no lysine [K]) kinase family, either directly or via the downstream SPAK/OSR1 Ste20-type ..
  30. San Cristobal P, Ponce Coria J, Vazquez N, Bobadilla N, Gamba G. WNK3 and WNK4 amino-terminal domain defines their effect on the renal Na+-Cl- cotransporter. Am J Physiol Renal Physiol. 2008;295:F1199-206 pubmed publisher
    Loss of physiological regulation of the renal thiazide-sensitive Na+-Cl- cotransporter (NCC) by mutant WNK1 or WNK4 results in pseudohypoaldosteronism type II (PHAII) characterized by arterial hypertension and hyperkalemia...
  31. Zhou B, Wang D, Feng X, Zhang Y, Wang Y, Zhuang J, et al. WNK4 inhibits NCC protein expression through MAPK ERK1/2 signaling pathway. Am J Physiol Renal Physiol. 2012;302:F533-9 pubmed publisher
    ..Mutations in two members of this family (WNK1 and WNK4) cause pseudohypoaldosteronism type II featuring hypertension, hyperkalemia, and metabolic acidosis...
  32. Park H, Kim J, Choi S, Lee Y, Zeng W, Kim K, et al. Serine-threonine kinase with-no-lysine 4 (WNK4) controls blood pressure via transient receptor potential canonical 3 (TRPC3) in the vasculature. Proc Natl Acad Sci U S A. 2011;108:10750-5 pubmed publisher
    Mutations in the serine-threonine kinase with-no-lysine 4 (WNK4) cause pseudohypoaldosteronism type 2 (PHAII), a Mendelian form of human hypertension...
  33. Rossier B, Staub O, Hummler E. Genetic dissection of sodium and potassium transport along the aldosterone-sensitive distal nephron: importance in the control of blood pressure and hypertension. FEBS Lett. 2013;587:1929-41 pubmed publisher
    ..This will allow to design rational strategies for the treatment of hypertension and for the development of the next generation of diuretics. ..
  34. Yang D, Li Q, So I, Huang C, Ando H, Mizutani A, et al. IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway. J Clin Invest. 2011;121:956-65 pubmed publisher
    ..They also have implications for WNK/SPAK kinase-regulated processes involved in systemic fluid homeostasis, hypertension, and cystic fibrosis. ..
  35. Chávez Canales M, Zhang C, Soukaseum C, Moreno E, Pacheco Alvarez D, Vidal Petiot E, et al. WNK-SPAK-NCC cascade revisited: WNK1 stimulates the activity of the Na-Cl cotransporter via SPAK, an effect antagonized by WNK4. Hypertension. 2014;64:1047-53 pubmed publisher
    The with-no-lysine (K) kinases, WNK1 and WNK4, are key regulators of blood pressure. Their mutations lead to familial hyperkalemic hypertension (FHHt), associated with an activation of the Na-Cl cotransporter (NCC)...
  36. Takahashi D, Mori T, Nomura N, Khan M, Araki Y, Zeniya M, et al. WNK4 is the major WNK positively regulating NCC in the mouse kidney. Biosci Rep. 2014;34: pubmed publisher
    ..However, the role of WNK4 in the regulation of NCC remains controversial. To address this, we generated and analysed WNK4-/- mice...
  37. Ponce Coria J, Markadieu N, Austin T, Flammang L, Rios K, Welling P, et al. A novel Ste20-related proline/alanine-rich kinase (SPAK)-independent pathway involving calcium-binding protein 39 (Cab39) and serine threonine kinase with no lysine member 4 (WNK4) in the activation of Na-K-Cl cotransporters. J Biol Chem. 2014;289:17680-8 pubmed publisher
    ..Serine threonine kinase WNK4 (With No K = lysine member 4) and members of the Ste20 kinase family, namely SPAK and OSR1 (Ste20-related proline/..
  38. Susa K, Sohara E, Rai T, Zeniya M, Mori Y, Mori T, et al. Impaired degradation of WNK1 and WNK4 kinases causes PHAII in mutant KLHL3 knock-in mice. Hum Mol Genet. 2014;23:5052-60 pubmed publisher
    ..hypertension, hyperkalemia and metabolic acidosis, and genes encoding with-no-lysine kinase 1 (WNK1) and WNK4 kinases are known to be responsible...
  39. Rozansky D, Cornwall T, Subramanya A, Rogers S, Yang Y, David L, et al. Aldosterone mediates activation of the thiazide-sensitive Na-Cl cotransporter through an SGK1 and WNK4 signaling pathway. J Clin Invest. 2009;119:2601-12 pubmed publisher
    ..The serine/threonine kinase with-no-lysine 4 (WNK4) has previously been shown to reduce cell surface expression of NCC...
  40. Vallon V. Regulation of the Na+-Cl- cotransporter by dietary NaCl: a role for WNKs, SPAK, OSR1, and aldosterone. Kidney Int. 2008;74:1373-5 pubmed publisher
  41. Shibata S, Rinehart J, Zhang J, Moeckel G, Castañeda Bueno M, Stiegler A, et al. Mineralocorticoid receptor phosphorylation regulates ligand binding and renal response to volume depletion and hyperkalemia. Cell Metab. 2013;18:660-71 pubmed publisher
    ..In volume depletion, angiotensin II and WNK4 signaling decrease MR(S843-P) levels, whereas hyperkalemia increases MR(S843-P)...
  42. Ring A, Cheng S, Leng Q, Kahle K, Rinehart J, Lalioti M, et al. WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo. Proc Natl Acad Sci U S A. 2007;104:4020-4 pubmed
    ..Previous work has shown that mutations in WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension with hyperkalemia, due to altered ..
  43. Fang Y, Yang S, Cheng C, Tseng M, Hsu H, Lin S. Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway. Sci Rep. 2016;6:18360 pubmed publisher
    ..We examined the role of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and with-no-lysine kinase 4 (WNK4) on expression of NCC in mouse models of CMA...
  44. Kahle K, MacGregor G, Wilson F, Van Hoek A, Brown D, Ardito T, et al. Paracellular Cl- permeability is regulated by WNK4 kinase: insight into normal physiology and hypertension. Proc Natl Acad Sci U S A. 2004;101:14877-82 pubmed
    ..Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension and hyperkalemia...
  45. Chu P, Cheng C, Wu Y, Fang Y, Chau T, Uchida S, et al. SPAK deficiency corrects pseudohypoaldosteronism II caused by WNK4 mutation. PLoS ONE. 2013;8:e72969 pubmed publisher
    ..b>Wnk4 (D561A/+) mice were crossed with kidney tubule-specific (KSP) Osr1 knockout (KSP-Osr1 (-/-)) and Spak knockout (..
  46. Kahle K, Wilson F, Leng Q, Lalioti M, O Connell A, Dong K, et al. WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion. Nat Genet. 2003;35:372-6 pubmed
    ..Positional cloning implicated the serine-threonine kinase WNK4 in this process; clustered mutations in PRKWNK4, encoding WNK4, cause hypertension and hyperkalemia (pseudohypoaldosteronism type II, PHAII) by altering renal ..
  47. Susa K, Sohara E, Takahashi D, Okado T, Rai T, Uchida S. WNK4 is indispensable for the pathogenesis of pseudohypoaldosteronism type II caused by mutant KLHL3. Biochem Biophys Res Commun. 2017;491:727-732 pubmed publisher
    ..It has been previously demonstrated that the amount of phosphorylated and total NCC markedly decreased in WNK4-/- mice, indicating that WNK4 plays a major role for activation of OSR1/SPAK-NCC signaling...
  48. Castañeda Bueno M, Cervantes Pérez L, Rojas Vega L, Arroyo Garza I, Vazquez N, Moreno E, et al. Modulation of NCC activity by low and high K(+) intake: insights into the signaling pathways involved. Am J Physiol Renal Physiol. 2014;306:F1507-19 pubmed publisher
    ..SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K(+)-citrate diets for 4 days...
  49. Shibata S, Arroyo J, Castañeda Bueno M, Puthumana J, Zhang J, Uchida S, et al. Angiotensin II signaling via protein kinase C phosphorylates Kelch-like 3, preventing WNK4 degradation. Proc Natl Acad Sci U S A. 2014;111:15556-61 pubmed publisher
    ..Mutations in the kinases with-no-lysine 4 (WNK4) or WNK1, or in either Cullin 3 (CUL3) or Kelch-like 3 (KLHL3)--components of an E3 ubiquitin ligase complex that ..
  50. Castañeda Bueno M, Arroyo J, Zhang J, Puthumana J, Yarborough O, Shibata S, et al. Phosphorylation by PKC and PKA regulate the kinase activity and downstream signaling of WNK4. Proc Natl Acad Sci U S A. 2017;114:E879-E886 pubmed publisher
    With-no-lysine kinase 4 (WNK4) regulates electrolyte homeostasis and blood pressure...