Wnk1

Summary

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

Top Publications

  1. Min X, Lee B, Cobb M, Goldsmith E. Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension. Structure. 2004;12:1303-11 pubmed
    ..Here we present the structure of the kinase domain of WNK1 at 1.8 A resolution, solved in a low activity conformation...
  2. 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...
  3. San Cristobal P, de los Heros P, Ponce Coria J, Moreno E, Gamba G. WNK kinases, renal ion transport and hypertension. Am J Nephrol. 2008;28:860-70 pubmed publisher
    ..The uncovered genes causing PHAII encode for serine/threonine kinases known as WNK1 and WNK4...
  4. Yang C, Liu X, Paliege A, Zhu X, Bachmann S, Dawson D, et al. WNK1 and WNK4 modulate CFTR activity. Biochem Biophys Res Commun. 2007;353:535-40 pubmed
    ..WNK kinases are widely expressed modulators of ion transport. WNK1 and WNK4, two WNK kinases that are mutated in familial hyperkalemic hypertension (FHHt), are co-expressed with CFTR ..
  5. 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...
  6. Moore T, Garg R, Johnson C, Coptcoat M, Ridley A, Morris J. PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and regulates actin cytoskeletal organization. J Biol Chem. 2000;275:4311-22 pubmed
    ..PSK is the first member of the STE20 family lacking a Cdc42/Rac binding domain that has been shown to regulate both the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and the actin cytoskeleton. ..
  7. Vorontsova I, Lam L, Delpire E, Lim J, Donaldson P. Identification of the WNK-SPAK/OSR1 signaling pathway in rodent and human lenses. Invest Ophthalmol Vis Sci. 2014;56:310-21 pubmed publisher
    ..WNK 1, 3, 4, SPAK, and OSR1 were identified at the transcript level in rat lenses and WNK1, 4, SPAK, and OSR1 expression confirmed at the protein level in both rat and human lenses...
  8. Vitari A, Deak M, Morrice N, Alessi D. The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases. Biochem J. 2005;391:17-24 pubmed
    Mutations in the human genes encoding WNK1 [with no K (lysine) protein kinase-1] and the related protein kinase WNK4 are the cause of Gordon's hypertension syndrome...
  9. Lazrak A, Liu Z, Huang C. Antagonistic regulation of ROMK by long and kidney-specific WNK1 isoforms. Proc Natl Acad Sci U S A. 2006;103:1615-20 pubmed
    ..Intronic deletions with increased expression of a ubiquitous long WNK1 transcript cause pseudohypoaldosteronism type 2 (PHA II), characterized by hypertension and hyperkalemia...

More Information

Publications30

  1. Heise C, Xu B, Deaton S, Cha S, Cheng C, Earnest S, et al. Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members. J Biol Chem. 2010;285:25161-7 pubmed publisher
    ..Mutations in two WNKs cause a heritable form of ion imbalance culminating in hypertension. WNK1 activates the serum- and glucocorticoid-induced protein kinase SGK1; the mechanism is noncatalytic...
  2. Wang Z, Yang C, Ellison D. Comparison of WNK4 and WNK1 kinase and inhibiting activities. Biochem Biophys Res Commun. 2004;317:939-44 pubmed
    WNK kinases are novel serine/threonine protein kinases. Mutations in two members of the WNK family, WNK1 and WNK4, cause familial hyperkalemic hypertension...
  3. Serysheva E, Berhane H, Grumolato L, Demir K, Balmer S, Bodak M, et al. Wnk kinases are positive regulators of canonical Wnt/?-catenin signalling. EMBO Rep. 2013;14:718-25 pubmed publisher
    ..Importantly, knockdown of human WNK1 and WNK2 also results in decreased Wnt signalling in mammalian cell culture, suggesting that Wnk kinases have a ..
  4. NARAY FEJES TOTH A, Snyder P, Fejes Toth G. The kidney-specific WNK1 isoform is induced by aldosterone and stimulates epithelial sodium channel-mediated Na+ transport. Proc Natl Acad Sci U S A. 2004;101:17434-9 pubmed
    b>WNK1 belongs to a unique family of Ser/Thr kinases that have been implicated in the control of blood pressure...
  5. Vitari A, Thastrup J, Rafiqi F, Deak M, Morrice N, Karlsson H, et al. Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1. Biochem J. 2006;397:223-31 pubmed
    ..Recent studies indicated that SPAK and OSR1 are phosphorylated and activated by the WNK1 [with no K (lysine) protein kinase-1] and WNK4, genes mutated in humans affected by Gordon's hypertension syndrome...
  6. 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...
  7. Moon T, Correa F, Kinch L, Piala A, Gardner K, Goldsmith E. Solution structure of the WNK1 autoinhibitory domain, a WNK-specific PF2 domain. J Mol Biol. 2013;425:1245-52 pubmed publisher
    b>WNK1 [with no lysine (K)-1] is a 250-kDa serine/threonine protein kinase involved in the maintenance of cellular salt levels and is directly linked to a hereditary form of hypertension...
  8. Tobin M, Raleigh S, Newhouse S, Braund P, Bodycote C, Ogleby J, et al. Association of WNK1 gene polymorphisms and haplotypes with ambulatory blood pressure in the general population. Circulation. 2005;112:3423-9 pubmed
    Blood pressure (BP) is a heritable trait of major public health concern. The WNK1 and WNK4 genes, which encode proteins in the WNK family of serine-threonine kinases, are involved in renal electrolyte homeostasis...
  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...
  10. Cope G, Murthy M, Golbang A, Hamad A, Liu C, Cuthbert A, et al. WNK1 affects surface expression of the ROMK potassium channel independent of WNK4. J Am Soc Nephrol. 2006;17:1867-74 pubmed
    ..Both WNK1 and WNK4 are expressed in the mammalian kidney, and mutations in either can cause the rare familial syndrome of ..
  11. 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...
  12. Piala A, Moon T, Akella R, He H, Cobb M, Goldsmith E. Chloride sensing by WNK1 involves inhibition of autophosphorylation. Sci Signal. 2014;7:ra41 pubmed publisher
    b>WNK1 [with no lysine (K)] is a serine-threonine kinase associated with a form of familial hypertension...
  13. 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...
  14. Dorwart M, Shcheynikov N, Wang Y, Stippec S, Muallem S. SLC26A9 is a Cl(-) channel regulated by the WNK kinases. J Physiol. 2007;584:333-45 pubmed
    ..Co-expression of SLC26A9 with the WNK kinases WNK1, WNK3 or WNK4 inhibited SLC26A9 activity, and the inhibition was independent of WNK kinase activity...
  15. Zhang Z, Li J, Wang Q, Zhao W, Hong J, Lou S, et al. WNK1 is involved in Nogo66 inhibition of OPC differentiation. Mol Cell Neurosci. 2015;65:135-42 pubmed publisher
    ..In our previous study, we found that LINGO-1 is associated with WNK1 in mediating Nogo-induced neurite extension inhibition by RhoA activation...
  16. Wang X, Tournier C. Regulation of cellular functions by the ERK5 signalling pathway. Cell Signal. 2006;18:753-60 pubmed
    ..The analysis of genetically modified mice in which the erk5 gene can be specifically deleted in certain tissues is shedding light into the physiological function of the ERK5 pathway during development and pathogenesis. ..
  17. 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...
  18. 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. ..
  19. Xu B, Min X, Stippec S, Lee B, Goldsmith E, Cobb M. Regulation of WNK1 by an autoinhibitory domain and autophosphorylation. J Biol Chem. 2002;277:48456-62 pubmed
    ..hypotheses about the position of the catalytic lysine, and we examined mechanisms involved in the regulation of WNK1 activity...
  20. 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...
  21. Xu B, English J, Wilsbacher J, Stippec S, Goldsmith E, Cobb M. WNK1, a novel mammalian serine/threonine protein kinase lacking the catalytic lysine in subdomain II. J Biol Chem. 2000;275:16795-801 pubmed
    We have cloned and characterized a novel mammalian serine/threonine protein kinase WNK1 (with no lysine (K)) from a rat brain cDNA library...