Wnk1

Summary

Gene Symbol: Wnk1
Description: WNK lysine deficient protein kinase 1
Alias: 6430573H23Rik, EG406236, Hsn2, Prkwnk1, mKIAA0344, serine/threonine-protein kinase WNK1, protein kinase lysine-deficient 1, protein kinase with no lysine 1
Species: mouse
Products:     Wnk1

Top Publications

  1. 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
    ..Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression...
  2. 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
    ..kinases (with 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...
  3. Choate K, Kahle K, Wilson F, Nelson Williams C, Lifton R. WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse Cl- -transporting epithelia. Proc Natl Acad Sci U S A. 2003;100:663-8 pubmed
    Mutations in WNK1 and WNK4, genes encoding members of a novel family of serine-threonine kinases, have recently been shown to cause pseudohypoaldosteronism type II (PHAII), an autosomal dominant disorder featuring hypertension, ..
  4. O Reilly M, Marshall E, Speirs H, Brown R. WNK1, a gene within a novel blood pressure control pathway, tissue-specifically generates radically different isoforms with and without a kinase domain. J Am Soc Nephrol. 2003;14:2447-56 pubmed
    b>WNK1 is a member of a novel serine/threonine kinase family, With-No-K, (lysine)...
  5. Vidal Petiot E, Cheval L, Faugeroux J, Malard T, Doucet A, Jeunemaitre X, et al. A new methodology for quantification of alternatively spliced exons reveals a highly tissue-specific expression pattern of WNK1 isoforms. PLoS ONE. 2012;7:e37751 pubmed publisher
    Mutations in the WNK1 gene, encoding a serine-threonine kinase of the WNK (With No lysine (K)) family, have been implicated in two rare human diseases, Familial Hyperkalemic Hypertension (FHHt) and Hereditary Sensory and Autonomic ..
  6. Delaloy C, Hadchouel J, Imbert Teboul M, Clemessy M, Houot A, Jeunemaitre X. Cardiovascular expression of the mouse WNK1 gene during development and adulthood revealed by a BAC reporter assay. Am J Pathol. 2006;169:105-18 pubmed
    Large deletions in WNK1 are associated with inherited arterial hypertension...
  7. 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
    b>WNK1 and WNK4 are unusual serine/threonine kinases with atypical positioning of the catalytic active-site lysine (WNK: With-No-K[lysine])...
  8. Sun X, Gao L, Yu R, Zeng G. Down-regulation of WNK1 protein kinase in neural progenitor cells suppresses cell proliferation and migration. J Neurochem. 2006;99:1114-21 pubmed
    b>WNK1, a Ser/Thr protein kinase, is widely expressed in many tissues. Its biological functions are largely unknown...
  9. Xie J, Wu T, Xu K, Huang I, Cleaver O, Huang C. Endothelial-specific expression of WNK1 kinase is essential for angiogenesis and heart development in mice. Am J Pathol. 2009;175:1315-27 pubmed publisher
    b>WNK1 [with-no-lysine (K)-1] is a ubiquitous serine/threonine kinase with a unique placement of the catalytic lysine residue...

More Information

Publications44

  1. Shekarabi M, Girard N, Rivi re J, Dion P, Houle M, Toulouse A, et al. Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II. J Clin Invest. 2008;118:2496-505 pubmed publisher
    ..We report here that HSN2 is a nervous system-specific exon of the with-no-lysine(K)-1 (WNK1) gene...
  2. Köchl R, Thelen F, Vanes L, Brazão T, Fountain K, Xie J, et al. WNK1 kinase balances T cell adhesion versus migration in vivo. Nat Immunol. 2016;17:1075-83 pubmed publisher
    ..Using an RNA-mediated interference screen, we identified the WNK1 kinase as a regulator of both integrin-mediated adhesion and T cell migration...
  3. Jiang Z, Zhou Q, Holik J, Patel S, Leszyk J, Coleman K, et al. Identification of WNK1 as a substrate of Akt/protein kinase B and a negative regulator of insulin-stimulated mitogenesis in 3T3-L1 cells. J Biol Chem. 2005;280:21622-8 pubmed
    ..Tryptic peptides from a 250-kDa immunoprecipitated protein were identified as the protein kinase WNK1 (with no lysine) by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, consistent with a ..
  4. Ding L, Zhang L, Kim M, Byzova T, Podrez E. Akt3 kinase suppresses pinocytosis of low-density lipoprotein by macrophages via a novel WNK/SGK1/Cdc42 protein pathway. J Biol Chem. 2017;292:9283-9293 pubmed publisher
    ..We now report that Akt3 constitutively suppresses macropinocytosis in macrophages through a novel WNK1/SGK1/Cdc42 pathway...
  5. Bergaya S, Faure S, Baudrie V, Rio M, Escoubet B, Bonnin P, et al. WNK1 regulates vasoconstriction and blood pressure response to ? 1-adrenergic stimulation in mice. Hypertension. 2011;58:439-45 pubmed publisher
    Gain-of-function mutations in the human WNK1 (with-no-lysine[K]1) gene are responsible for a monogenic form of arterial hypertension, and WNK1 polymorphisms have been associated with common essential hypertension...
  6. Elvira Matelot E, Zhou X, Farman N, Beaurain G, Henrion Caude A, Hadchouel J, et al. Regulation of WNK1 expression by miR-192 and aldosterone. J Am Soc Nephrol. 2010;21:1724-31 pubmed publisher
    b>WNK1 and WNK4 encode two members of the WNK serine-threonine kinase subfamily. Greater WNK1 expression associates with higher BP...
  7. Zeng G, Gao L, Xia T, Gu Y, Yu R. Expression of the mouse WNK1 gene in correlation with ganglioside GD3 and functional analysis of the mouse WNK1 promoter. Gene. 2005;344:233-9 pubmed
    b>WNK1 is one of WNK (With No K=Lysine) protein kinases which comprise a newly described subfamily...
  8. 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...
  9. Lee B, Chen W, Stippec S, Cobb M. Biological cross-talk between WNK1 and the transforming growth factor beta-Smad signaling pathway. J Biol Chem. 2007;282:17985-96 pubmed
    ..Here we describe a biological link between WNKs and transforming growth factor (TGF) beta-Smad signaling. Both WNK1 and WNK4 directly bind to and phosphorylate Smad2...
  10. 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
    ..by salt-sensitive hypertension, hyperkalemia and metabolic acidosis, and genes encoding with-no-lysine kinase 1 (WNK1) and WNK4 kinases are known to be responsible...
  11. 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. ..
  12. Yu G, Cheng M, Wang W, Zhao R, Liu Z. Involvement of WNK1-mediated potassium channels in the sexual dimorphism of blood pressure. Biochem Biophys Res Commun. 2017;485:255-260 pubmed publisher
    ..BK) channel and Na-K-2Cl cotransporter (NKCC2) as well as the upstream regulator with-no-lysine kinase 1 (WNK1) enhanced in female mice under normal condition...
  13. Cheng C, Baum M, Huang C. Kidney-specific WNK1 regulates sodium reabsorption and potassium secretion in mouse cortical collecting duct. Am J Physiol Renal Physiol. 2013;304:F397-402 pubmed publisher
    Kidney-specific with-no-lysine kinase 1 (KS-WNK1) is a kinase-deficient variant of WNK1 that is expressed exclusively in the kidney...
  14. Dbouk H, Weil L, Perera G, Dellinger M, Pearson G, Brekken R, et al. Actions of the protein kinase WNK1 on endothelial cells are differentially mediated by its substrate kinases OSR1 and SPAK. Proc Natl Acad Sci U S A. 2014;111:15999-6004 pubmed publisher
    ..In mice, global as well as endothelial-specific WNK1 gene disruption results in embryonic lethality due to angiogenic and cardiovascular defects...
  15. 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 ..
  16. Vidal Petiot E, Elvira Matelot E, Mutig K, Soukaseum C, Baudrie V, Wu S, et al. WNK1-related Familial Hyperkalemic Hypertension results from an increased expression of L-WNK1 specifically in the distal nephron. Proc Natl Acad Sci U S A. 2013;110:14366-71 pubmed publisher
    Large deletions in the first intron of the With No lysine (K) 1 (WNK1) gene are responsible for Familial Hyperkalemic Hypertension (FHHt), a rare form of human hypertension associated with hyperkalemia and hyperchloremic metabolic ..
  17. Liu Y, Song X, Shi Y, Shi Z, Niu W, Feng X, et al. WNK1 activates large-conductance Ca2+-activated K+ channels through modulation of ERK1/2 signaling. J Am Soc Nephrol. 2015;26:844-54 pubmed publisher
    ..In this study, we investigated the effect of WNK1 on BK channel activity...
  18. Roy A, Al Qusairi L, Donnelly B, Ronzaud C, Marciszyn A, Gong F, et al. Alternatively spliced proline-rich cassettes link WNK1 to aldosterone action. J Clin Invest. 2015;125:3433-48 pubmed publisher
    ..Here, we have shown that aldosterone activates SPAK/OSR1 via WNK1. We identified 2 alternatively spliced exons embedded within a proline-rich region of WNK1 that contain PY motifs, ..
  19. Hadchouel J, Soukaseum C, Büsst C, Zhou X, Baudrie V, Zürrer T, et al. Decreased ENaC expression compensates the increased NCC activity following inactivation of the kidney-specific isoform of WNK1 and prevents hypertension. Proc Natl Acad Sci U S A. 2010;107:18109-14 pubmed publisher
    Mutations in WNK1 and WNK4 lead to familial hyperkalemic hypertension (FHHt)...
  20. Lafreniere R, MacDonald M, Dube M, MacFarlane J, O Driscoll M, Brais B, et al. Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the Study of Canadian Genetic Isolates. Am J Hum Genet. 2004;74:1064-73 pubmed
    ..This gene, termed "HSN2," consists of a single exon located within intron 8 of the PRKWNK1 gene and is transcribed from the same strand...
  21. Sato A, Shibuya H. WNK signaling is involved in neural development via Lhx8/Awh expression. PLoS ONE. 2013;8:e55301 pubmed publisher
    ..Some mutations in human WNK1 or WNK4 are associated with Pseudohypoaldosteronism type II, a form of hypertension...
  22. Webb T, Carrisoza Gaytán R, Montalbetti N, Rued A, Roy A, Socovich A, et al. Cell-specific regulation of L-WNK1 by dietary K. Am J Physiol Renal Physiol. 2016;310:F15-26 pubmed publisher
    ..This disorder is linked to mutations in genes encoding with-no-lysine kinase 1 (WNK1), WNK4, and Kelch-like 3/Cullin 3, two components of an E3 ubiquitin ligase complex that degrades WNKs...
  23. 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...
  24. Susa K, Kita S, Iwamoto T, Yang S, Lin S, Ohta A, et al. Effect of heterozygous deletion of WNK1 on the WNK-OSR1/ SPAK-NCC/NKCC1/NKCC2 signal cascade in the kidney and blood vessels. Clin Exp Nephrol. 2012;16:530-8 pubmed
    ..However, the pathogenic effect of intronic deletions in WNK1 genes also observed in PHAII patients remains unclear...
  25. Liu Z, Xie J, Wu T, Truong T, Auchus R, Huang C. Downregulation of NCC and NKCC2 cotransporters by kidney-specific WNK1 revealed by gene disruption and transgenic mouse models. Hum Mol Genet. 2011;20:855-66 pubmed publisher
    b>WNK1 (with-no-lysine[K]-1) is a protein kinase of which mutations cause a familial hypertension and hyperkalemia syndrome known as pseudohypoaldosteronism type 2 (PHA2)...
  26. Liu Z, Wang H, Huang C. Regulation of ROMK channel and K+ homeostasis by kidney-specific WNK1 kinase. J Biol Chem. 2009;284:12198-206 pubmed publisher
    WNK kinases are serine-threonine kinases with an atypical placement of the catalytic lysine. WNK1, the first member discovered, has multiple alternatively spliced isoforms, including a ubiquitously expressed full-length long form (L-WNK1) ..
  27. 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
  28. Shekarabi M, Lafrenière R, Gaudet R, Laganiere J, Marcinkiewicz M, Dion P, et al. Comparative analysis of the expression profile of Wnk1 and Wnk1/Hsn2 splice variants in developing and adult mouse tissues. PLoS ONE. 2013;8:e57807 pubmed publisher
    ..b>WNK1 has been shown to have different isoforms due to what seems to be largely tissue specific splicing...
  29. Xie J, Yoon J, Yang S, Lin S, Huang C. WNK1 protein kinase regulates embryonic cardiovascular development through the OSR1 signaling cascade. J Biol Chem. 2013;288:8566-74 pubmed publisher
    b>WNK1 is a widely expressed serine/threonine protein kinase that regulates multiple cellular and organ functions via diverse mechanisms...
  30. 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)...
  31. Vinciguerra M. Aldosterone, but not increased Na+ influx or NF-kappaB activation, increases kidney-specific WNK1 gene expression in renal collecting duct cells. Horm Metab Res. 2009;41:67-70 pubmed publisher
  32. Cheng C, Truong T, Baum M, Huang C. Kidney-specific WNK1 inhibits sodium reabsorption in the cortical thick ascending limb. Am J Physiol Renal Physiol. 2012;303:F667-73 pubmed publisher
    Kidney-specific WNK1 (KS-WNK1) is a variant of full-length WNK1. Previous studies have reported that KS-WNK1 is predominantly expressed in the distal convoluted tubule (DCT) where it regulates sodium-chloride cotransporter...
  33. Friedel P, Kahle K, Zhang J, Hertz N, Pisella L, Buhler E, et al. WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons. Sci Signal. 2015;8:ra65 pubmed publisher
    ..We showed that the serine-threonine kinase WNK1 [with no lysine (K)] forms a physical complex with KCC2 in the developing mouse brain...
  34. Kahle K, Schmouth J, Lavastre V, Latremoliere A, Zhang J, Andrews N, et al. Inhibition of the kinase WNK1/HSN2 ameliorates neuropathic pain by restoring GABA inhibition. Sci Signal. 2016;9:ra32 pubmed publisher
    ..The HSN2-containing splice variant is referred to as WNK1/HSN2...
  35. Subramanya A, Yang C, Zhu X, Ellison D. Dominant-negative regulation of WNK1 by its kidney-specific kinase-defective isoform. Am J Physiol Renal Physiol. 2006;290:F619-24 pubmed
    With-no-lysine kinase-1 (WNK1) gene mutations cause familial hyperkalemic hypertension (FHHt), a Mendelian disorder of excessive renal Na+ and K+ retention...