WNK4

Summary

Gene Symbol: WNK4
Description: WNK lysine deficient protein kinase 4
Alias: PHA2B, PRKWNK4, serine/threonine-protein kinase WNK4, protein kinase lysine-deficient 4, protein kinase with no lysine 4
Species: human

Top Publications

  1. ncbi WNK4 regulates airway Na+ transport: study of familial hyperkalaemia and hypertension
    Z Farfel
    Department of Medicine, Tel Aviv University, Tel Aviv, Israel
    Eur J Clin Invest 35:410-5. 2005
  2. doi [Association of the C1155547T polymorphism in WNK4 gene with essential hypertension in Xinjiang Kazakhs]
    Fei Fei Cao
    Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, Shandong, P R China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 27:546-9. 2010
  3. doi Hypertension associated polymorphisms in WNK1/WNK4 are not associated with hydrochlorothiazide response
    Yunfeng Han
    Department of Geriatrics, the Military General Hospital of Beijing PLA, Beijing, China
    Clin Biochem 44:1045-9. 2011
  4. ncbi Human hypertension caused by mutations in WNK kinases
    F H Wilson
    Howard Hughes Medical Institute Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06510 USA
    Science 293:1107-12. 2001
  5. ncbi WNK kinases, a novel protein kinase subfamily in multi-cellular organisms
    F Verissimo
    Centre for Human Genetics, National Institute of Health Dr Ricardo Jorge, Lisbon, Portugal
    Oncogene 20:5562-9. 2001
  6. ncbi Genetic variants of WNK4 in whites and African Americans with hypertension
    Porat M Erlich
    Department of Medicine, Boston University School of Medicine, Boston, Mass, USA
    Hypertension 41:1191-5. 2003
  7. pmc WNK4 regulates apical and basolateral Cl- flux in extrarenal epithelia
    Kristopher T Kahle
    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 101:2064-9. 2004
  8. ncbi WNK4 intron 10 polymorphism is not associated with hypertension
    Helen J L Speirs
    Basic and Clinical Genomics Laboratory, School of Medical Sciences and Institute of Biomedical Research, University of Sydney, NSW, Australia
    Hypertension 43:766-8. 2004
  9. ncbi Three novel missense mutations of WNK4, a kinase mutated in inherited hypertension, in Japanese hypertensives: implication of clinical phenotypes
    Kei Kamide
    Division of Hypertension and Nephrology, National Cardiovascular Center, 5 7 1 Fujishirodai, Suita, Osaka 565 8565, Japan
    Am J Hypertens 17:446-9. 2004
  10. ncbi Hypercalciuria in familial hyperkalemia and hypertension accompanies hyperkalemia and precedes hypertension: description of a large family with the Q565E WNK4 mutation
    Haim Mayan
    Department of Medicine E, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Hashomer 52621, Israel
    J Clin Endocrinol Metab 89:4025-30. 2004

Research Grants

  1. Sodium Chloride Cotransporter Regulation by WNK Kinase
    Hui Cai; Fiscal Year: 2010
  2. Hui Cai; Fiscal Year: 2016
  3. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
  4. WenHui Wang; Fiscal Year: 2016
  5. Robert S Hoover; Fiscal Year: 2015
  6. The Function of Claudin-7 in Renal Epithelial Cells
    Yan Hua Chen; Fiscal Year: 2012
  7. Alicia A McDonough; Fiscal Year: 2016
  8. Chao Ling Yang; Fiscal Year: 2016
  9. Jesse Rinehart; Fiscal Year: 2014
  10. The Role of Ubiquitin in Sodium Chloride Co-Transporter Regulation
    BENJAMIN S KO; Fiscal Year: 2012

Scientific Experts

Detail Information

Publications160 found, 100 shown here

  1. ncbi WNK4 regulates airway Na+ transport: study of familial hyperkalaemia and hypertension
    Z Farfel
    Department of Medicine, Tel Aviv University, Tel Aviv, Israel
    Eur J Clin Invest 35:410-5. 2005
    WNK [With No K (lysine)] kinases are essential for regulation of blood pressure and potassium homeostasis. WNK4 expression was recently found not only in the distal nephron but also in chloride-transporting epithelia...
  2. doi [Association of the C1155547T polymorphism in WNK4 gene with essential hypertension in Xinjiang Kazakhs]
    Fei Fei Cao
    Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, Shandong, P R China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 27:546-9. 2010
    To investigate whether the WNK lysine deficient protein kinase 4 (WNK4) gene C1155547T polymorphism is associated with essential hypertension (EH) in Xinjiang Kazakhs and to assess the effect of the interaction between this polymorphism ..
  3. doi Hypertension associated polymorphisms in WNK1/WNK4 are not associated with hydrochlorothiazide response
    Yunfeng Han
    Department of Geriatrics, the Military General Hospital of Beijing PLA, Beijing, China
    Clin Biochem 44:1045-9. 2011
    Our purpose was to investigate whether with-no-K[Lys] kinase (WNK) 1 and WNK4 genetic polymorphisms are associated with both hypertension and diuretics response.
  4. ncbi Human hypertension caused by mutations in WNK kinases
    F H Wilson
    Howard Hughes Medical Institute Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06510 USA
    Science 293:1107-12. 2001
    ..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...
  5. ncbi WNK kinases, a novel protein kinase subfamily in multi-cellular organisms
    F Verissimo
    Centre for Human Genetics, National Institute of Health Dr Ricardo Jorge, Lisbon, Portugal
    Oncogene 20:5562-9. 2001
    ..Three additional, partial human protein kinase sequences, WNK2, WNK3 and WNK4, are also reported here with catalytic domains that are 95% homologous to WNK1...
  6. ncbi Genetic variants of WNK4 in whites and African Americans with hypertension
    Porat M Erlich
    Department of Medicine, Boston University School of Medicine, Boston, Mass, USA
    Hypertension 41:1191-5. 2003
    ..This region contains the WNK4 gene that causes the mendelian disorder pseudohypoaldosteronism type II, characterized by high potassium levels and ..
  7. pmc WNK4 regulates apical and basolateral Cl- flux in extrarenal epithelia
    Kristopher T Kahle
    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 101:2064-9. 2004
    Mutations in the serine-threonine kinase WNK4 [with no lysine (K) 4] cause pseudohypoaldosteronism type II, a Mendelian disease featuring hypertension with hyperkalemia...
  8. ncbi WNK4 intron 10 polymorphism is not associated with hypertension
    Helen J L Speirs
    Basic and Clinical Genomics Laboratory, School of Medical Sciences and Institute of Biomedical Research, University of Sydney, NSW, Australia
    Hypertension 43:766-8. 2004
    A polymorphism in intron 10 of the serine-threonine kinase with no lysine (K) 4 gene WNK4 (G-->A, base 1156666 on chromosome 17) has recently been associated with essential hypertension in a white American population...
  9. ncbi Three novel missense mutations of WNK4, a kinase mutated in inherited hypertension, in Japanese hypertensives: implication of clinical phenotypes
    Kei Kamide
    Division of Hypertension and Nephrology, National Cardiovascular Center, 5 7 1 Fujishirodai, Suita, Osaka 565 8565, Japan
    Am J Hypertens 17:446-9. 2004
    Mutations in serine-threonine kinase WNK4 with no lysine (K) at a key catalytic residue cause familial hypertension known as pseudohypoaldosteronism type II (PHAII)...
  10. ncbi Hypercalciuria in familial hyperkalemia and hypertension accompanies hyperkalemia and precedes hypertension: description of a large family with the Q565E WNK4 mutation
    Haim Mayan
    Department of Medicine E, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Hashomer 52621, Israel
    J Clin Endocrinol Metab 89:4025-30. 2004
    ..WNK1 kinase overexpression and WNK4 kinase inactivating missense mutations cause FHH...
  11. doi WNK4 polymorphisms and essential hypertension in the Uyghur population
    Ming Lu
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
    Clin Exp Hypertens 31:179-85. 2009
    ..polymorphisms (T1155547C at exon7, G1155942T at exon8, G1156666A at intron10, and C1163527T at intron14) of WNK4 (with-no-kinase) gene on the prevalence of essential hypertension in a Chinese minority ethnic group-the Uyghur ..
  12. doi Association of Ala589Ser polymorphism of WNK4 gene with essential hypertension in a high-risk Chinese population
    Zhi Jun Sun
    Department of Medical Genetics, China Medical University, Shenyang, 110001, China
    J Physiol Sci 59:81-6. 2009
    ..between particular single nucleotide polymorphisms of serine-threonine kinase with no lysine (K) 4 gene (WNK4) and essential hypertension have yielded controversial results...
  13. ncbi [Study on the association between genetic polymorphism on WNK4 genes and essential hypertension among Kazakhs ethnic population, in Xinjiang]
    Fei Fei Cao
    Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan 250012, China
    Zhonghua Liu Xing Bing Xue Za Zhi 31:375-8. 2010
    To investigate whether G1155942T polymorphism in WNK4 gene is associated with essential hypertension in a population with Kazakhs ethnicity, in Xinjiang.
  14. doi A WNK4 gene variant relates to osteoporosis and not to hypertension in the Portuguese population
    Ana Isabel Mendes
    Departamento de Genetica, Instituto Nacional de Saude Dr Ricardo Jorge, Lisboa, Portugal
    Mol Genet Metab 102:465-9. 2011
    Germline mutations in the WNK4 gene originate Gordon syndrome or pseudohypoaldosteronism type II, a familial form of hypertension with hyperkalemia and hypercalciuria...
  15. pmc The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction
    Akihito Ohta
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 451:111-22. 2013
    ..Interestingly, the equivalent region in WNK4 encompasses residues that are mutated in Gordon's syndrome patients...
  16. doi Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension
    Mai Wakabayashi
    Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo, Tokyo 113 8519, Japan
    Cell Rep 3:858-68. 2013
    ..Here, we found that KLHL3 interacted with Cullin3 and WNK4, induced WNK4 ubiquitination, and reduced the WNK4 protein level...
  17. pmc Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4
    Shigeru Shibata
    Department of Genetics, Howard Hughes Medical Institute, and W M Keck Facility, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 110:7838-43. 2013
    ..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...
  18. pmc Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation
    Guojin Wu
    Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 0006, USA
    FEBS Lett 587:1717-22. 2013
    Mutations in with-no-lysine (K) kinase 4 (WNK4) and a ubiquitin E3 ligase complex component kelch-like 3 (KLHL3) both cause pseudohypoaldosteronism II (PHAII), a hereditary form of hypertension...
  19. doi KLHL2 interacts with and ubiquitinates WNK kinases
    Daiei Takahashi
    Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan
    Biochem Biophys Res Commun 437:457-62. 2013
    Mutations in the WNK1 and WNK4 genes result in an inherited hypertensive disease, pseudohypoaldosteronism type II (PHAII). Recently, the KLHL3 and Cullin3 genes were also identified as responsible genes for PHAII...
  20. doi Decrease of WNK4 ubiquitination by disease-causing mutations of KLHL3 through different molecular mechanisms
    Yutaro Mori
    Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo, Tokyo 113 8519, Japan
    Biochem Biophys Res Commun 439:30-4. 2013
    Recently, we demonstrated that WNK4 is a substrate for KLHL3-Cullin3 (CUL3) E3 ubiquitin ligase complexes and that impaired WNK4 ubiquitination is a common mechanism for pseudohypoaldosteronism type II (PHAII) caused by WNK4, KLHL3, and ..
  21. pmc WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse Cl- -transporting epithelia
    Keith A Choate
    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 100:663-8. 2003
    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, ..
  22. pmc Regulation of ENaC-mediated sodium transport by glucocorticoids in Reissner's membrane epithelium
    Sung Huhn Kim
    Kansas State Univ, Anatomy and Physiology, 228 Coles Hall, Manhattan, KS 66506 5802, USA
    Am J Physiol Cell Physiol 296:C544-57. 2009
    ..3-fold), KCNK1 ( approximately 3-fold), 11beta-HSD1 ( approximately 2-fold), SGK1 ( approximately 2-fold), and WNK4 ( approximately 3-fold)...
  23. pmc A new locus on chromosome 12p13.3 for pseudohypoaldosteronism type II, an autosomal dominant form of hypertension
    S Disse-Nicodeme
    INSERM U36, College de France, Paris
    Am J Hum Genet 67:302-10. 2000
    ..Two loci have previously been mapped at low resolution to chromosome 1q31-42 (PHA2A) and 17p11-q21 (PHA2B)...
  24. pmc WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1)
    Qiang Leng
    Department of Molecular and Cellular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA
    J Physiol 571:275-86. 2006
    ..1) to maintain renal NaCl and K+ homeostasis; mutations in PRKWNK4, encoding WNK4, cause a Mendelian disease featuring hypertension and hyperkalemia...
  25. ncbi Conserved synteny in rat and mouse for a blood pressure QTL on human chromosome 17
    Heike Zimdahl
    Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Hypertension 39:1050-2. 2002
    ..It is of interest that this region also contains Wnk4, a gene previously identified to cause pseudohypoaldosteronism type II and human hypertension...
  26. pmc Intersectin links WNK kinases to endocytosis of ROMK1
    Guocheng He
    Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8856, USA
    J Clin Invest 117:1078-87. 2007
    ..Mutations of 2 family members, WNK1 and WNK4, cause pseudohypoaldosteronism type 2 (PHA2), an autosomal-dominant disease characterized by hypertension and ..
  27. pmc WNK kinases regulate thiazide-sensitive Na-Cl cotransport
    Chao Ling Yang
    Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Clin Invest 111:1039-45. 2003
    ..Mutations in two members of the WNK kinase family, WNK1 and WNK4, cause the disease...
  28. ncbi WNK4 kinase is a negative regulator of K+-Cl- cotransporters
    Tomas Garzon-Muvdi
    Molecular Physiology Unit, Vasco de Quiroga No 15, Tlalpan 14000, Mexico City, Mexico
    Am J Physiol Renal Physiol 292:F1197-207. 2007
    ..b>WNK4 inhibits the activity of NCC and NKCC1, while in the presence of the STE20-related proline-alanine-rich kinase SPAK ..
  29. ncbi WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1
    Tetsuo Moriguchi
    Department of Molecular Cell Biology, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, and CREST, JST, Chiyoda, Tokyo 101 0062
    J Biol Chem 280:42685-93. 2005
    The WNK1 and WNK4 genes have been found to be mutated in some patients with hyperkalemia and hypertension caused by pseudohypoaldosteronism type II...
  30. doi Mechanisms for hypercalciuria in pseudohypoaldosteronism type II-causing WNK4 knock-in mice
    Sung Sen Yang
    Division of Nephrology, Department of Medicine, Tri Service General Hospital, and School of Medicine, National Defense Medical Center, Neihu 114, Taipei, Taiwan
    Endocrinology 151:1829-36. 2010
    The mechanisms underlying hypercalciuria in pseudohypoaldosteronism type II (PHAII) caused by WNK4 mutations remain unclear...
  31. ncbi Increased urinary Na-Cl cotransporter protein in familial hyperkalaemia and hypertension
    Haim Mayan
    Department of Medicine E, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Hashomer 52621 Israel
    Nephrol Dial Transplant 23:492-6. 2008
    ..termed pseudohypoaldosteronism type II, is a rare monogenic form of hypertension caused by mutations in the WNK1 or WNK4 kinases...
  32. ncbi Association of WNK1 gene polymorphisms and haplotypes with ambulatory blood pressure in the general population
    Martin D Tobin
    Department of Health Sciences, University of Leicester, Leicester, England
    Circulation 112:3423-9. 2005
    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...
  33. pmc WNK3 and WNK4 amino-terminal domain defines their effect on the renal Na+-Cl- cotransporter
    Pedro San-Cristobal
    Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Vasco de Quiroga No 15, Tlalpan 14000, Mexico City, Mexico
    Am J Physiol Renal Physiol 295:F1199-206. 2008
    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...
  34. doi Targeted disruption of the Wnk4 gene decreases phosphorylation of Na-Cl cotransporter, increases Na excretion and lowers blood pressure
    Akihito Ohta
    Department of Nephrology, Tokyo Medical and Dental University, Japan
    Hum Mol Genet 18:3978-86. 2009
    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...
  35. doi Mechanisms of type I and type II pseudohypoaldosteronism
    Seth B Furgeson
    Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver, 12700 E 19th Avenue, C281, Aurora, CO 80045, USA
    J Am Soc Nephrol 21:1842-5. 2010
    ..PHAII is the result of mutations in a family of serine-threonine kinases called with-no-lysine kinases (WNK)1 and WNK4. WNK4 negatively regulates the NaCl cotransporter (NCC), and PHAII mutations in WNK4 abrogate this affect...
  36. ncbi Properties of WNK1 and implications for other family members
    Lisa Y Lenertz
    Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    J Biol Chem 280:26653-8. 2005
    ..Of the four human WNK family members, WNK1 and WNK4 have been linked to a hereditary form of hypertension, pseudohypoaldosteronism type II...
  37. pmc WNK lies upstream of kinases involved in regulation of ion transporters
    Gerardo Gamba
    Molecular Physiology Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Universidad Nacional Autonoma de Mexico, Tlalpan 14000, Mexico City, Mexico
    Biochem J 391:e1-3. 2005
    Two members of a recently discovered family of protein kinases {WNK1 and WNK4 [with no K (lysine) kinases-1 and -4]} are the cause of an inherited disease known as pseudohypoaldosteronism type II that features arterial hypertension...
  38. doi Pathophysiological roles of WNK kinases in the kidney
    Shinichi Uchida
    Department of Nephrology, Tokyo Medical and Dental University, Yushima, Bunkyo ku, Tokyo, Japan
    Pflugers Arch 460:695-702. 2010
    Since the discovery of mutations in the WNK1 and WNK4 genes in pseudohypoaldosteronism type II (PHAII), the pathophysiological role of WNK kinases in hypertension and renal ion transport has been a hot topic for investigation...
  39. pmc WNK4 kinase stimulates caveola-mediated endocytosis of TRPV5 amplifying the dynamic range of regulation of the channel by protein kinase C
    Seung Kuy Cha
    Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8856, USA
    J Biol Chem 285:6604-11. 2010
    b>WNK4 (with-no-lysine (K) kinase-4) is present in the distal nephron of the kidney and plays an important role in the regulation of renal ion transport...
  40. pmc The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex
    Chao Ling Yang
    Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Clin Invest 117:3403-11. 2007
    ..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...
  41. pmc Molecular components of signal amplification in olfactory sensory cilia
    Thomas Hengl
    Department of Molecular Physiology, University of Heidelberg, 69120 Heidelberg, Germany
    Proc Natl Acad Sci U S A 107:6052-7. 2010
    ..on the kinases SPAK and OSR1, which are enriched in the cilia together with their own activating kinases, WNK1 and WNK4. A second Cl(-) transporter, the Cl(-)/HCO(3)(-) exchanger SLC4A1, is expressed in the cilia and may support Cl(-) ..
  42. ncbi Regulation of the expression of the Na/Cl cotransporter by WNK4 and WNK1: evidence that accelerated dynamin-dependent endocytosis is not involved
    Amir P Golbang
    Department of Medicine, University of Cambridge, UK
    Am J Physiol Renal Physiol 291:F1369-76. 2006
    ..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...
  43. ncbi Dietary electrolyte-driven responses in the renal WNK kinase pathway in vivo
    Michelle O'Reilly
    Centre for Cardiovascular Science, Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh, UK EH16 4TJ
    J Am Soc Nephrol 17:2402-13. 2006
    WNK1 and WNK4 are unusual serine/threonine kinases with atypical positioning of the catalytic active-site lysine (WNK: With-No-K[lysine])...
  44. doi WNK kinases and essential hypertension
    Chou Long Huang
    Department of Medicine, Division of Nephrology, UT Southwestern Medical Center, Dallas, Texas 75390 8856, USA
    Curr Opin Nephrol Hypertens 17:133-7. 2008
    ..The present review summarizes recent literature and discusses the potential roles of WNKs in the pathogenesis of essential hypertension...
  45. pmc Molecular determinants of hyperosmotically activated NKCC1-mediated K+/K+ exchange
    Kenneth B Gagnon
    Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Physiol 588:3385-96. 2010
    ..Under isosmotic conditions or with activation of the kinases SPAK/WNK4, the NKCC1-mediated Cl(-) uptake in Xenopus laevis oocytes, as measured using (36)Cl, is twice the value of K(+) ..
  46. doi Effect of angiotensin II on the WNK-OSR1/SPAK-NCC phosphorylation cascade in cultured mpkDCT cells and in vivo mouse kidney
    Gulibaha Talati
    Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1 5 45 Yushima Bunkyo, Tokyo 113 8519, Japan
    Biochem Biophys Res Commun 393:844-8. 2010
    In our recent study using Wnk4(D561A/+) knockin mice, we determined that the WNK-OSR1/SPAK-NaCl cotransporter (NCC) phosphorylation cascade is important for regulating NCC function in vivo...
  47. pmc On the substrate recognition and negative regulation of SPAK, a kinase modulating Na+-K+-2Cl- cotransport activity
    Kenneth B Gagnon
    Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Am J Physiol Cell Physiol 299:C614-20. 2010
    ..We found that WNK4 is capable of stimulating the deletion mutant when S321 is present, but not when S321 is mutated into an alanine.
  48. pmc Heritable forms of hypertension
    V Matti Vehaskari
    Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA 70118, USA
    Pediatr Nephrol 24:1929-37. 2009
    ..syndrome, with mutations in two regulatory kinases [with no lysine (K) serine/threonine protein kinases (WNK)1 or WNK4]; and apparent mineralocorticoid excess (AME), with an inactivating mutation in the glucocorticoid-metabolizing ..
  49. ncbi Comparison of WNK4 and WNK1 kinase and inhibiting activities
    Zhaohong Wang
    Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, OR 97239, USA
    Biochem Biophys Res Commun 317:939-44. 2004
    WNK kinases are novel serine/threonine protein kinases. Mutations in two members of the WNK family, WNK1 and WNK4, cause familial hyperkalemic hypertension...
  50. pmc Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1
    Alberto C Vitari
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 397:223-31. 2006
    ..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...
  51. ncbi Apoptosis-associated tyrosine kinase scaffolding of protein phosphatase 1 and SPAK reveals a novel pathway for Na-K-2C1 cotransporter regulation
    Kenneth B E Gagnon
    Department of Anesthesiology, Vanderbilt University Medical Center, Nasvhille, TN 37232 2520, USA
    Am J Physiol Cell Physiol 292:C1809-15. 2007
    ..With no lysine (K) kinase (WNK4) has also been implicated in the regulation of NKCC1 activity through upstream activation of SPAK...
  52. ncbi Cloning, genomic organization, alternative splicing and expression analysis of the human gene WNK3 (PRKWNK3)
    Simon Holden
    Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke s Hospital Box 139, Hills Road, Cambridge, CB2 2XY, UK
    Gene 335:109-19. 2004
    ..and CR3 contain highly conserved residues which have been shown to be important for the normal function of WNK1 and WNK4, and CR2 contains a highly conserved 22 amino acid motif specific to chordate species...
  53. ncbi Role of WNK kinases in regulating tubular salt and potassium transport and in the development of hypertension
    Gerardo Gamba
    Molecular Physiology Unit, Instituto de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No 15, Tlalpan 14000, Mexico City, Mexico
    Am J Physiol Renal Physiol 288:F245-52. 2005
    ..Two of these genes, WNK1 and WNK4 located in human chromosomes 12 and 17, respectively, are responsible for PHA-II...
  54. ncbi Dominant-negative regulation of WNK1 by its kidney-specific kinase-defective isoform
    Arohan R Subramanya
    Division of Nephrology and Hypertension, Oregon Health and Science University, PP262, 3314 SW US Veterans Hospital Road, Portland, OR 97239, USA
    Am J Physiol Renal Physiol 290:F619-24. 2006
    ..Through its catalytic activity, full-length kinase-sufficient WNK1 (L-WNK1) suppresses its paralog, WNK4, thereby upregulating thiazide-sensitive Na-Cl cotransporter (NCC) activity...
  55. ncbi Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway
    F Verissimo
    Centro de Genética Humana, Instituto Nacional de Saude Dr Ricardo Jorge, Lisboa, Portugal
    Oncogene 25:4172-82. 2006
    ..subfamily of WNK (with no K= lysine) protein kinases has four human members and germline mutations in the WNK1 and WNK4 genes were recently found to cause pseudohypoaldosteronism type II, a familial hypertension disease...
  56. ncbi Role of with-no-lysine [K] kinases in the pathogenesis of Gordon's syndrome
    Jian Xie
    Department of Medicine, Room J5 104, MC 8856, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390 8856, USA
    Pediatr Nephrol 21:1231-6. 2006
    ..Recent positional cloning has linked mutations of WNK1 and WNK4 to Gordon's syndrome...
  57. ncbi Cellular mechanisms of WNK4-mediated regulation of ion transport proteins in the distal tubule
    J B Peng
    Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294 0017, USA
    Kidney Int 69:2116-8. 2006
    Gene mutations in WNK4 kinase cause a genetic form of hypertension by affecting multiple ion transport pathways through different mechanisms. Cai et al...
  58. ncbi WNK1 affects surface expression of the ROMK potassium channel independent of WNK4
    Georgina Cope
    Department of Medicine, University of Cambridge, Cambridge, UK
    J Am Soc Nephrol 17:1867-74. 2006
    ..Both WNK1 and WNK4 are expressed in the mammalian kidney, and mutations in either can cause the rare familial syndrome of hypertension ..
  59. ncbi Molecular physiology of the WNK kinases
    Kristopher T Kahle
    Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
    Annu Rev Physiol 70:329-55. 2008
    Mutations in the serine-threonine kinases WNK1 and WNK4 cause a Mendelian disease featuring hypertension and hyperkalemia...
  60. doi A novel protein kinase signaling pathway essential for blood pressure regulation in humans
    Kristopher T Kahle
    Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Trends Endocrinol Metab 19:91-5. 2008
    The discovery that mutations in WNK4 [encoding a member of the WNK family - so named because of the unique substitution of cysteine for lysine at a nearly invariant residue within subdomain II of its catalytic core: with no K (lysine)] ..
  61. pmc Characterization of the kinase activity of a WNK4 protein complex
    Robert Ahlstrom
    Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California 90089, USA
    Am J Physiol Renal Physiol 297:F685-92. 2009
    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...
  62. pmc Aldosterone mediates activation of the thiazide-sensitive Na-Cl cotransporter through an SGK1 and WNK4 signaling pathway
    David J Rozansky
    Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA
    J Clin Invest 119:2601-12. 2009
    ..The serine/threonine kinase with-no-lysine 4 (WNK4) has previously been shown to reduce cell surface expression of NCC...
  63. pmc WNK4 enhances the degradation of NCC through a sortilin-mediated lysosomal pathway
    Bo Zhou
    Second Affiliated Hospital, Wenzhou Medical College, Zhejiang, China
    J Am Soc Nephrol 21:82-92. 2010
    WNK kinase is a serine/threonine kinase that plays an important role in electrolyte homeostasis. WNK4 significantly inhibits the surface expression of the sodium chloride co-transporter (NCC) by enhancing the degradation of NCC through a ..
  64. doi Emerging roles for WNK kinases in cancer
    Sónia Moniz
    Departamento de Genetica, Instituto Nacional de Saude Dr Ricardo Jorge, Lisbon, Portugal
    Cell Mol Life Sci 67:1265-76. 2010
    ..Although most research has focussed on the role of WNK1, WNK3 and WNK4 in regulating different ion transporters in both the kidney and extrarenal tissues, there is growing evidence for ..
  65. pmc Altered expression of regulators of the cortical chloride transporters NKCC1 and KCC2 in schizophrenia
    Dominique Arion
    Department of Psychiatry, University of Pittsburgh, PA 15213, USA
    Arch Gen Psychiatry 68:21-31. 2011
    ..The activities of these transporters are in turn regulated by a network of serine-threonine kinases that includes OXSR1, STK39, and the WNK kinases WNK1, WNK3, and WNK4.
  66. doi The activity of the thiazide-sensitive Na(+)-Cl(-) cotransporter is regulated by protein phosphatase PP4
    Mark Glover
    Department of Medicine, University of Cambridge, UK
    Can J Physiol Pharmacol 88:986-95. 2010
    ..There are 2 phosphorylation-controlled regulatory pathways for NCC: type 1, mediated by WNK4 and affecting trafficking to the surface membrane, and type 2, affecting intrinsic transporter kinetics by ..
  67. pmc Antagonistic regulation of cystic fibrosis transmembrane conductance regulator cell surface expression by protein kinases WNK4 and spleen tyrosine kinase
    Ana Isabel Mendes
    Departamento de Genetica, Instituto Nacional de Saude Dr Ricardo Jorge, Avenida Padre Cruz, 1649 016 Lisbon, Portugal
    Mol Cell Biol 31:4076-86. 2011
    ..the cell surface expression of the cystic fibrosis transmembrane conductance regulator (CFTR) is also regulated by WNK4 in mammalian cells...
  68. doi Functional insights into the activation mechanism of Ste20-related kinases
    Kenneth B Gagnon
    Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232 2520, USA
    Cell Physiol Biochem 28:1219-30. 2011
    ..Heterologous expression of sea urchin OSR1 (suOSR1) cRNA with mouse WNK4 cRNA and mouse NKCC1 cRNA in Xenopus laevisoocytes activated the cotransporter indicating evolutionary conservation ..
  69. pmc Disease-causing mutations in the acidic motif of WNK4 impair the sensitivity of WNK4 kinase to calcium ions
    Tao Na
    Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 0006, USA
    Biochem Biophys Res Commun 419:293-8. 2012
    b>WNK4 is a serine/threonine protein kinase that is involved in pseudohypoaldosteronism type II (PHAII), a Mendelian form disorder featuring hypertension and hyperkalemia...
  70. doi Pathophysiology of salt sensitivity hypertension
    Katsuyuki Ando
    Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
    Ann Med 44:S119-26. 2012
    ..Renal beta2 adrenoceptor stimulation in the kidney leads to decreased transcription of the gene encoding WNK4, a negative regulator of Na(+) reabsorption through Na(+) -Cl (-) cotransporter in the distal convoluted tubules, ..
  71. pmc A new model of the distal convoluted tubule
    Benjamin Ko
    Department of Medicine, University of Chicago, Chicago, Illinois, USA
    Am J Physiol Renal Physiol 303:F700-10. 2012
    ..Importantly, they display release of WNK4 inhibition of NCC by small hairpin RNA knockdown...
  72. doi Loss of WNK3 is compensated for by the WNK1/SPAK axis in the kidney of the mouse
    Katharina Mederle
    Institute of Physiology, Univ of Regensburg, Universitätsstr 31, 93040 Regensburg, Germany
    Am J Physiol Renal Physiol 304:F1198-209. 2013
    ..54). WNK1 was markedly upregulated in WNK3-deficient mice, whereas the expression of WNK4 was similar in both genotypes. When the mice were fed a salt-restricted diet [0...
  73. pmc Molecular evidence for a role for K(+)-Cl(-) cotransporters in the kidney
    Zesergio Melo
    Molecular Physiology Unit, Vasco de Quiroga No 15, Tlalpan 14000, Mexico City, Mexico
    Am J Physiol Renal Physiol 305:F1402-11. 2013
    ..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...
  74. pmc In silico analysis and experimental verification of OSR1 kinase - Peptide interaction
    Thomas M Austin
    Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States
    J Struct Biol 187:58-65. 2014
    ..recognizes a unique peptide motif present in OSR1- and SPAK-activating kinases (with-no-lysine kinase 1 (WNK1) and WNK4) as well as their substrates (NKCC1, NKCC2, and NCC)...
  75. doi WNK-SPAK-NCC cascade revisited: WNK1 stimulates the activity of the Na-Cl cotransporter via SPAK, an effect antagonized by WNK4
    Maria Chavez-Canales
    From the Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico M C C, M C B, N V, L R V, G G Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico M C C, E M, M C B, N V, L R V, G G Division of Nephrology and Hypertension, Oregon Health and Science University, Portland C Z, N P M, S R, X J, C L Y, D H E INSERM UMR970 Paris Cardiovascular Research Center, Paris, France C S, E V P, X J, J H Faculty of Medicine, University Paris Descartes, Sorbonne Paris Cité, Paris, France C S, E V P, Polish-American Children's Hospital
    Hypertension 64:1047-53. 2014
    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)...
  76. pmc Angiotensin II signaling via protein kinase C phosphorylates Kelch-like 3, preventing WNK4 degradation
    Shigeru Shibata
    Departments of Genetics and Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173 8605, Japan and Department of Clinical Epigenetics, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153 0041, Japan Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510
    Proc Natl Acad Sci U S A 111:15556-61. 2014
    ..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 ..
  77. doi Gordon Syndrome: a continuing story
    Kevin M O'shaughnessy
    Division of Experimental Medicine and Immunotherapeutics, Department of Medicine, Addenbrooke s Hospital University of Cambridge, Cambridge, CB2 2QQ UK
    Pediatr Nephrol 30:1903-8. 2015
    ..In 2001, mutations in genes encoding two serine/threonine kinases, WNK1 and WNK4, were identified as causing GS...
  78. pmc The Effect of WNK4 on the Na+-Cl- Cotransporter Is Modulated by Intracellular Chloride
    Silvana Bazúa-Valenti
    Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico
    J Am Soc Nephrol 26:1781-6. 2015
    ..of the renal Na(+)-Cl(-) cotransporter (NCC) because of altered regulation by with no-lysine-kinase 1 (WNK1) or WNK4. The effect of WNK4 on NCC, however, has been controversial because both inhibition and activation have been ..
  79. pmc Mechanisms of angiotensin II stimulation of NCC are time-dependent in mDCT15 cells
    Benjamin Ko
    Department of Medicine, University of Chicago, Chicago, Illinois
    Am J Physiol Renal Physiol 308:F720-7. 2015
    ..ANG II has been implicated as a switch that turns WNK4 from an inhibitor of NCC into an activator of NCC, and ANG II's effect on NCC appears to require WNK4...
  80. pmc Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway
    Xiuyan Feng
    Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
    Am J Physiol Renal Physiol 308:F1119-27. 2015
    ..Previous studies reported that dietary salts modulated NCC abundance through either WNK4 [with no lysine (k) kinase 4]-SPAK (Ste20-related proline alanine-rich kinase) or WNK4-extracellular signal-..
  81. pmc Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway
    Junichi Maruyama
    Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Sci Rep 6:18710. 2016
    ..In this report, we identified WNK4 as an interacting partner of a recently identified MAP3K, apoptosis signal-regulating kinase 3 (ASK3)...
  82. doi The regulation of Na+Cl- cotransporter by with-no-lysine kinase 4
    Eduardo R Argaiz
    Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
    Curr Opin Nephrol Hypertens 25:417-23. 2016
    Abundant evidence supports that the NaCl cotransporter (NCC) activity is tightly regulated by the with-no-lysine (WNK) kinases. Here, we summarize the data regarding NCC regulation by WNKs, with a particular emphasis on WNK4.
  83. ncbi WNK kinases and the control of blood pressure
    Georgina Cope
    Clinical Pharmacology Unit, Department of Medicine, University of Cambridge, Cambridge, UK
    Pharmacol Ther 106:221-31. 2005
    ..Two WNK isoforms, WNK1 and WNK4, have been identified as the disease genes for a rare monogenic hypertension syndrome (Gordon's syndrome or ..
  84. ncbi WNK4, as thiazides, shuts off NaCl reabsorption to stimulate Na/K exchange
    Francois Verrey
    Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Nephrol Dial Transplant 22:1305-8. 2007
  85. pmc Protein phosphatase 1 modulates the inhibitory effect of With-no-Lysine kinase 4 on ROMK channels
    Dao Hong Lin
    Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA
    Am J Physiol Renal Physiol 303:F110-9. 2012
    With-no-Lysine kinase 4 (WNK4) inhibited ROMK (Kir1.1) channels and the inhibitory effect of WNK4 was abolished by serum-glucocorticoid-induced kinase 1 (SGK1) but restored by c-Src...
  86. pmc Aldosterone does not require angiotensin II to activate NCC through a WNK4-SPAK-dependent pathway
    Nils van der Lubbe
    Department of Internal Medicine, Erasmus Medical Center, PO Box 2040, Room D 405, 3000 CA, Rotterdam, The Netherlands
    Pflugers Arch 463:853-63. 2012
    We and others have recently shown that angiotensin II can activate the sodium chloride cotransporter (NCC) through a WNK4-SPAK-dependent pathway...
  87. pmc WNK signaling is involved in neural development via Lhx8/Awh expression
    Atsushi Sato
    Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
    PLoS ONE 8:e55301. 2013
    ..Some mutations in human WNK1 or WNK4 are associated with Pseudohypoaldosteronism type II, a form of hypertension...
  88. ncbi Resolution of hypertension during pregnancy in familial hyperkalemia and hypertension with the WNK4 Q565E mutation
    Haim Mayan
    Department of Medicine E, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Hashomer, Israel
    Am J Obstet Gynecol 192:598-603. 2005
    ..hypertension is familial hyperkalemia and hypertension, which is caused by mutations in the kinases WNK1 or WNK4 and other unknown molecular defects...
  89. ncbi Regulation of blood pressure, the epithelial sodium channel (ENaC), and other key renal sodium transporters by chronic insulin infusion in rats
    Jian Song
    Division of Endocrinology and Metabolism, Department of Medicine, Georgetown Univ, 4000 Reservoir Rd 233 NW, Washington, DC 20057 1412, USA
    Am J Physiol Renal Physiol 290:F1055-64. 2006
    ..In addition, insulin decreased cortical "with no lysine" kinase (WNK4) abundance (by 16% relative to control), which may have increased NCC activity...
  90. pmc Effects of rare and common blood pressure gene variants on essential hypertension: results from the Family Blood Pressure Program, CLUE, and Atherosclerosis Risk in Communities studies
    Khanh Dung H Nguyen
    Center for Complex Disease Genomics, McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Circ Res 112:318-26. 2013
    ..Hypertension affects ≈30% of adults in industrialized countries and is the major risk factor for cardiovascular disease...
  91. pmc A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo
    Katsuyuki Oi
    Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    Biol Open 1:120-7. 2012
    Mutations in WNK1 and WNK4 kinase genes have been shown to cause a human hereditary hypertensive disease, pseudohypoaldosteronism type II (PHAII)...
  92. pmc Phosphorylation regulates NCC stability and transporter activity in vivo
    Sung Sen Yang
    Division of Nephrology, Department of Medicine, Tri Service General Hospital, Taipei, Taiwan
    J Am Soc Nephrol 24:1587-97. 2013
    ..When Wnk4(D561A/+) mice, a model of pseudohypoaldosteronism type II expressing an activated Spak/Osr1-Ncc, were crossed with ..
  93. pmc Regulation of large-conductance Ca2+-activated K+ channels by WNK4 kinase
    Zhijian Wang
    Renal Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
    Am J Physiol Cell Physiol 305:C846-53. 2013
    ..With-no-lysine kinase 4 (WNK4) is a serine-threonine kinase expressed in the distal nephron that inhibits ROMK activity and renal K(+) secretion...
  94. pmc Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4
    Frederick H Wilson
    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 100:680-4. 2003
    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 ..
  95. ncbi The role of Wnk4 in polygenic hypertension: a candidate gene analysis on rat chromosome 10
    Jan Monti
    Max Delbrück Center for Molecular Medicine MDC, Robert Rossle Str 10, 13092 Berlin, Germany
    Hypertension 41:938-42. 2003
    ..b>Wnk4, a gene previously identified to cause pseudohypoaldosteronism type II, a rare mendelian form of arterial ..
  96. ncbi [Monogenic hypertension]
    Volker Bahr
    Abteilung für Endokrinologie, Diabetologie und Ernährungsmedizin, Medizinische Klinik IV, Klinikum Benjamin Franklin, Freie Universitat Berlin
    Med Klin (Munich) 98:208-17. 2003
    ..Mutations in the serine-threonine kinases WNK1 or WNK4 cause pseudohypoaldosteronism type II. WNK1 and WNK4 are expressed in the distal part of the nephron...
  97. ncbi [Correlation analysis between WNK4 gene and essential hypertension]
    Zhi Jun Sun
    Department of Genetics, China Medical University, Shenyang 110001, China
    Zhongguo Yi Xue Ke Xue Yuan Xue Bao 25:145-8. 2003
    To investigate association of mutation in WNK4 gene with essential hypertension and to analyze the expression of WNK4 gene.
  98. ncbi WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion
    Kristopher T Kahle
    Howard Hughes Medical Institute, 300 Cedar Street, TAC S 341D, and Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Nat Genet 35:372-6. 2003
    ..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 ..
  99. ncbi WNK1 activates ERK5 by an MEKK2/3-dependent mechanism
    Bing E Xu
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 279:7826-31. 2004
    ..Mutations in human WNK1 and WNK4 have been implicated in causing a familial form of hypertension...
  100. ncbi WNK1 phosphorylates synaptotagmin 2 and modulates its membrane binding
    Byung Hoon Lee
    Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 15:741-51. 2004
    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...
  101. pmc Paracellular Cl- permeability is regulated by WNK4 kinase: insight into normal physiology and hypertension
    Kristopher T Kahle
    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 101:14877-82. 2004
    ..Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension and hyperkalemia...

Research Grants26

  1. Sodium Chloride Cotransporter Regulation by WNK Kinase
    Hui Cai; Fiscal Year: 2010
    ..Mutations in WNK1 and WNK4 kinases are found to cause pseudohypoaldosteronism type II (PHA II), also referred to as Gordon syndrome...
  2. Hui Cai; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The aim of this proposal is to elucidate the mechanism of how WNK4 regulates Maxi K channel function. WNK (with no lysine (K)) kinase is a subfamily of serine/threonine kinases (5)...
  3. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
    ..Mutations in either WNK1 or WNK4 cause pseudohypoaldosteronism type II (PHA II), a form of high blood pressure caused by mutation of a single gene...
  4. WenHui Wang; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): With-No-Lysine Kinase 4 (WNK4) plays an important role in regulating Na and K transport in the aldosterone-sensitive distal nephron (ASDN)...
  5. Robert S Hoover; Fiscal Year: 2015
    ..With-No-Lysine Kinase 1 and 4 (WNK1 and WNK4), Ste20-related proline alanine-rich kinase (SPAK) and Oxidative Stress Response-1 (OSR1) are also important ..
  6. The Function of Claudin-7 in Renal Epithelial Cells
    Yan Hua Chen; Fiscal Year: 2012
    ..Mutations in WNK4 kinase have been linked to hypertension in pseudohypoaldosteronism type II (PHAII)...
  7. Alicia A McDonough; Fiscal Year: 2016
    ..The renin angiotensin system (RAS) stimulates NCC activity via an AngII-WNK4-SPAK dependent pathway...
  8. Chao Ling Yang; Fiscal Year: 2016
    ..WNK1, WNK3, and WNK4 have distinct properties to stimulate or inhibit salt transport, effects that can be modified based on ..
  9. Jesse Rinehart; Fiscal Year: 2014
    ..studies on the K-Cl cotransporters as a representative direct mediator of electrolyte flux and the kinases Wnk1 and Wnk4 as critical signaling components of ion flux...
  10. The Role of Ubiquitin in Sodium Chloride Co-Transporter Regulation
    BENJAMIN S KO; Fiscal Year: 2012
    ..Previous studies have reported decreased NCC activity in response to the presence of WNK4 (a kinase associated with a form of genetic hypertension called Gordon's Syndrome) and phorbol esters (..
  11. Tianxin Yang; Fiscal Year: 2016
    ..further employ molecular and electrophysiological approaches to determine ENaC as the molecular target of PGE2 and WNK4-mediated paracellular transport as the molecular target of PPAR...
  12. Novel Ca receptor signaling pathways for control of renal ion transport
    Richard Tyler Miller; Fiscal Year: 2012
    ..The project has three specific aims: Aim 1. Define the mechanism by which the CaR activates WNK1 and WNK4. Cell surface expression (biotinylation) and channel density (whole cell patch) will be used as measures of CaR ..
  13. Coordination of Renal K and Na Transport by Vesicle Traffic
    James B Wade; Fiscal Year: 2013
    ..We expect to answer the following specific questions: 1) What is the role of SPAK and WNK4 phosphorylation in activation of NCC in the kidney? 2) How do WNKs modulate SPAK-Dependent regulation of NCC?
  14. EPITHELIAL OXALATE AND CITRATE TRANSPORT
    DAVID BRUCE MOUNT; Fiscal Year: 2011
    ..We.will also determine the functional consequences of coding sequence variation in WNK4, a novel kinase with potent inhibitory effects on both SLC26A2 and SLC26A6, apical oxalate exchangers in the small ..
  15. REGULATION OF THE SODIUM CHLORIDE COTRANSPORTER
    Robert S Hoover; Fiscal Year: 2010
    ..This proposal will test the hypothesis that PKC and WNK4 kinase play a key role in regulation of NCC, predominantly by phosphorylation of serine and threonine residues ..
  16. Mechanisms of Regulation of Anion Exchanger SLC26A6
    Hatim A Hassan; Fiscal Year: 2010
    ..SLC26A6 was also remarkably suppressed (with reduced surface and total protein expression) when WNK4 was co-expressed in oocytes. A closely related anion transporter, Pendrin (SLC26A4), was unaffected by PKC or WNK4...
  17. WNK1 regulation of renal NaCl cotransport
    Arohan Subramanya; Fiscal Year: 2006
    ..FHHt is caused by mutations in the serine-threonine kinases WNK1 and WNK4, proteins highly expressed in the renal distal convoluted tubule (DCT)...
  18. RENAL POTASSIUM TRANSPORT IN PHYSIOLOGY AND DISEASES
    Chou Long Huang; Fiscal Year: 2005
    ..The biochemical studies will be correlated with electrophysiological recording of channel activity. ..
  19. Modulation of K channels in renal collecting duct
    Wen Hui Wang; Fiscal Year: 2007
    ....
  20. PATHOBIOLOGY OF CEREBRAL CAVERNOUS MALFORMATION
    Richard Lifton; Fiscal Year: 2002
    ..They have established a collection of these lesions and have begun developing cell cultures of different cell lines from lesions in order to pursue this aim. ..
  21. Sickle Red Cell K+ Transporter Genetics in S. cerevisiae
    Seth Alper; Fiscal Year: 2002
    ..3) (Provisional Aim): Time permitting, to improve, validate, and standardize growth rescue of trk1delta/trk2delta S. cerevisiae by expression in nonpermissive conditions of cDNA encoding the mammalian IK1 K(ca) channel. ..
  22. ION CHANNEL REGULATION BY THE CYTOPLASMIC TAIL OF PDK1
    Seth Alper; Fiscal Year: 2005
    ..We will search for novel interacting proteins, and prepare protein suitable for structural analysis. ..
  23. RBC Ion Transporters as Hemoglobinopathy Risk Modifiers
    Seth Alper; Fiscal Year: 2009
    ..The proposed experiments will increase understanding of sickle cell disease and thalassemia by providing mouse models for genetic tests of new drug therapies under development for near-term clinical testing. ..
  24. MOLECULAR PHYSIOLOGY OF BAND 3 LIKE PROTEINS OF KIDNEY
    Seth Alper; Fiscal Year: 2007
    ..5. Define aspects of transcriptional and translational regulation of AE gene products in kidney of mutant and parental mouse strains and in cultured kidney cells. ..
  25. Prenatal and Perinatal Programming of Adult Hypertension
    VESA VEHASKARI; Fiscal Year: 2006
    ..The effect of short-term postnatal dietary and phamacological manipulations on the long-term blood pressure profile will be investigated. ..
  26. Advances in Renal Research: Human Diseases of Protein Processing
    David Ellison; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..