WNK4

Summary

Gene Symbol: WNK4
Description: WNK lysine deficient protein kinase 4
Alias: PHA2B, PRKWNK4, protein kinase lysine-deficient 4, protein kinase with no lysine 4, serine/threonine-protein kinase WNK4
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. ncbi SLC26A9 is a Cl(-) channel regulated by the WNK kinases
    Michael R Dorwart
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9040, USA
    J Physiol 584:333-45. 2007
  3. ncbi Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members
    Charles J Heise
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 285:25161-7. 2010
  4. ncbi [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
  5. ncbi Serine-threonine kinase with-no-lysine 4 (WNK4) controls blood pressure via transient receptor potential canonical 3 (TRPC3) in the vasculature
    Hyun Woo Park
    Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120 752, Korea
    Proc Natl Acad Sci U S A 108:10750-5. 2011
  6. ncbi 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
  7. ncbi 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
  8. ncbi 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
  9. ncbi 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
  10. 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

Research Grants

  1. Function of STE20 Related Protein Kinases
    Melanie Cobb; Fiscal Year: 2007
  2. REGULATION OF THE SODIUM CHLORIDE COTRANSPORTER
    Robert Hoover; Fiscal Year: 2007
  3. Sodium Chloride Cotransporter Regulation by WNK Kinase
    Hui Cai; Fiscal Year: 2006
  4. Coordination of Renal K and Na Transport by Vesicle Traffic
    James B Wade; Fiscal Year: 2010
  5. The Function of Claudin-7 in Renal Epithelial Cells
    Yan Hua Chen; Fiscal Year: 2009
  6. The Function of Claudin-7 in Renal Epithelial Cells
    Yan Hua Chen; Fiscal Year: 2010
  7. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2010
  8. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie Cobb; Fiscal Year: 2009
  9. Genetic determinants of urine lithogenicity
    JOHN LIESKE; Fiscal Year: 2009
  10. Genetic determinants of urine lithogenicity
    JOHN LIESKE; Fiscal Year: 2009

Scientific Experts

Detail Information

Publications119 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. ncbi SLC26A9 is a Cl(-) channel regulated by the WNK kinases
    Michael R Dorwart
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9040, USA
    J Physiol 584:333-45. 2007
    ..Co-expression of SLC26A9 with the WNK kinases WNK1, WNK3 or WNK4 inhibited SLC26A9 activity, and the inhibition was independent of WNK kinase activity...
  3. ncbi Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members
    Charles J Heise
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 285:25161-7. 2010
    ..The N termini of the WNKs also have the capacity to interact with SGK1. More detailed analysis of activation by WNK4 suggests mechanisms in common with WNK1...
  4. ncbi [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 ..
  5. ncbi Serine-threonine kinase with-no-lysine 4 (WNK4) controls blood pressure via transient receptor potential canonical 3 (TRPC3) in the vasculature
    Hyun Woo Park
    Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120 752, Korea
    Proc Natl Acad Sci U S A 108:10750-5. 2011
    Mutations in the serine-threonine kinase with-no-lysine 4 (WNK4) cause pseudohypoaldosteronism type 2 (PHAII), a Mendelian form of human hypertension...
  6. ncbi 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, ..
  7. ncbi 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)...
  8. ncbi 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)...
  9. ncbi 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...
  10. 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...
  11. ncbi 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 ..
  12. 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 ..
  13. ncbi 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...
  14. 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...
  15. 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...
  16. ncbi 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...
  17. 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...
  18. ncbi 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...
  19. ncbi 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...
  20. ncbi 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...
  21. 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...
  22. 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 ..
  23. ncbi 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...
  24. ncbi 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...
  25. ncbi 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...
  26. 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...
  27. ncbi 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...
  28. ncbi 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)] ..
  29. 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...
  30. ncbi 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...
  31. ncbi 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(-) ..
  32. 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...
  33. 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])...
  34. ncbi 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(+) ..
  35. ncbi 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...
  36. ncbi 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...
  37. ncbi 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.
  38. ncbi 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 ..
  39. ncbi 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...
  40. 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...
  41. ncbi 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...
  42. ncbi 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 ..
  43. 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...
  44. ncbi Regulation of NKCC2 by a chloride-sensing mechanism involving the WNK3 and SPAK kinases
    Jose Ponce-Coria
    Molecular Physiology Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán and Instituto de Investigaciones Biomédicas, Universidad Nacional Autonoma de Mexico, Tlalpan, 14000 Mexico City, Mexico
    Proc Natl Acad Sci U S A 105:8458-63. 2008
    ..activation of NKCC2 requires the interaction of two serine-threonine kinases, WNK3 (related to WNK1 and WNK4, genes mutated in a Mendelian form of hypertension) and SPAK (a Ste20-type kinase known to interact with and ..
  45. ncbi Mechanism of regulation of renal ion transport by WNK kinases
    Chou Long Huang
    Department of Medicine, Division of Nephrology, UT Southwestern Medical Center, Dallas, Texas 75390 8856, USA
    Curr Opin Nephrol Hypertens 17:519-25. 2008
    ..This review summarizes recent advances in the understanding of the mechanism of regulation of renal ion transport by WNK kinases...
  46. ncbi A patient with pseudohypoaldosteronism type II caused by a novel mutation in WNK4 gene
    Hui Gong
    Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Lu, Shanghai 200025, People s Republic of China
    Endocrine 33:230-4. 2008
    ..However, these features were absent in his parents. Sequencing analysis found the patient with a WNK4 gene mutation, 1682 C > T in Exon 7, which resulted a missense mutation at codon 561 (P561L)...
  47. ncbi Upregulation of human with-no-lysine kinase-4 gene expression by GATA-1 acetylation
    Miao Li
    Department of Medical Genetics, China Medical University, No92, Bei Er Road, Shenyang 110001, China
    Int J Biochem Cell Biol 41:872-8. 2009
    With-no-lysine kinase-4 (WNK4), a member of the serine-threonine protein kinase family, acts as a multifunctional regulator of diverse ion transporters...
  48. ncbi Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone
    Motoko Chiga
    Department of Nephrology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
    Kidney Int 74:1403-9. 2008
    Pseudohypoaldosteronism type II (PHAII) is caused by mutations in the WNK1 and WNK4 genes (WNK with-no-lysine kinase)...
  49. ncbi Familial hyperkalemia and hypertension: pathogenetic insights based on lithium clearance
    Haim Mayan
    Department of Medicine E, Sheba Medical Center, Tel Hashomer, Israel
    J Clin Endocrinol Metab 94:3010-6. 2009
    ..Familial hyperkalemia and hypertension (FHHt) is caused by mutations in WNK kinases. Its pathogenesis is not completely understood...
  50. ncbi Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway
    Pedro San-Cristobal
    Molecular Physiology Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Universidad Nacional Autonoma de Mexico, Tlalpan 14000 Mexico City, Mexico
    Proc Natl Acad Sci U S A 106:4384-9. 2009
    Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and high serum K(+) levels (hyperkalemia)...
  51. ncbi Epigenetic silencing of the kinase tumor suppressor WNK2 is tumor-type and tumor-grade specific
    Peter Jun
    Department of Neurological Surgery, University of California, San Francisco, Cancer Center, Room N225, 2340 Sutter St, San Francisco, CA 94143, USA
    Neuro Oncol 11:414-22. 2009
    ..MEK1 (mitogen-activated protein kinase kinase 1), and point mutations have been reported in WNK1, WNK2, WNK3, and WNK4. In meningiomas, WNK2 was aberrantly methylated in 83% and 71% of grade II and III meningiomas, respectively, but ..
  52. ncbi Molecular physiology of the thiazide-sensitive sodium-chloride cotransporter
    Benjamin Ko
    Department of Medicine, University of Chicago, Chicago, Illinois, USA
    Curr Opin Nephrol Hypertens 18:421-7. 2009
    ..This review summarizes recent advances in the understanding of the molecular physiology and regulation of the thiazide-sensitive sodium-chloride cotransporter (NCC)...
  53. ncbi Multigene kinase network, kidney transport, and salt in essential hypertension
    Paul A Welling
    Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    Kidney Int 77:1063-9. 2010
    ..network minimally includes the Ste20-related proline-alanine-rich kinase (SPAK), the with-no-lysine kinases (WNKs), WNK4 and WNK1, and their effectors, the thiazide-sensitive NaCl cotransporter and the potassium secretory channel, ROMK...
  54. ncbi [The effect of aldosterone A on renal potassium excretion]
    Signe Abitz Winther
    Nefrologisk Klinik P 2131, Rigshospitalet, Denmark
    Ugeskr Laeger 173:126-9. 2011
    ..WNK1 (L-WNK1), the shorter kidney specific WNK1 transcript (KS-WNK1), formed by alternative splicing, and WNK4. Aldosterone activates expression of KS-WNK1 and inhibits WNK4 via SGK1 - both leading to stimulation of ENaC and ..
  55. ncbi 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...
  56. ncbi Effects of potassium on expression of renal sodium transporters in salt-sensitive hypertensive rats induced by uninephrectomy
    Ji Yong Jung
    Department of Internal Medicine, Gachon University of Medicine and Science, Incheon, Korea
    Am J Physiol Renal Physiol 300:F1422-30. 2011
    ..b>WNK4 mRNA expression was significantly increased in the HS+KCl group (1.4-fold of control at 1 wk and 1...
  57. ncbi Phenotypes of pseudohypoaldosteronism type II caused by the WNK4 D561A missense mutation are dependent on the WNK-OSR1/SPAK kinase cascade
    Motoko Chiga
    Department of Nephrology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    J Cell Sci 124:1391-5. 2011
    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)...
  58. ncbi Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans
    Margus Putku
    Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
    Hum Mutat 32:806-14. 2011
    Mutations in WNK1 and WNK4 cause familial hypertension, the Gordon syndrome. WNK1 and WNK4 conserved noncoding regions were targeted to polymorphism screening using DHPLC and DGGE...
  59. ncbi WNK4 kinase inhibits Maxi K channel activity by a kinase-dependent mechanism
    Jieqiu Zhuang
    Department of Nephrology, The Second Affiliated Hospital, Wenzhou Medical College, Zhejiang, China
    Am J Physiol Renal Physiol 301:F410-9. 2011
    ..Recent studies showed that both WNK1 and WNK4 inhibit ROMK activity...
  60. ncbi 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.
  61. ncbi WNK2 kinase is a novel regulator of essential neuronal cation-chloride cotransporters
    Jesse Rinehart
    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 286:30171-80. 2011
    ..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 ..
  62. ncbi Familial renal tubular acidosis
    Seth L Alper
    Renal Division and Molecular and Vascular Medicine Division, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Nephrol 23:S57-76. 2010
    ..pseudohypoaldosteronism type 2 [PHA2]) is caused by dominant gain-of-function mutations in the kinases WNK1 and WNK4. Hyperkalemic RTA accompanied by volume depletion is caused by loss-of-function mutations in genes encoding the ..
  63. ncbi WNK4 kinase negatively regulates the surface expression of muscarinic M3 receptor
    Woo Young Chung
    Department of Pharmacology and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120 752, Republic of Korea
    Cell Signal 23:566-71. 2011
    With-No-Lysine [K] 4 (WNK4) kinase regulates the surface expression of various ion transporters...
  64. ncbi Immunolocalization of WNK4 in mouse kidney
    Mayuko Ohno
    Department of Medicine, Kidney Center, Tokyo Women s Medical University, 8 1 Kawada cho, Shinjyuku ku, Tokyo, Japan
    Histochem Cell Biol 136:25-35. 2011
    Initial reports claim that WNK4 localization is mainly at intercellular junctions of distal convoluted tubules (DCT) and cortical collecting ducts (CCD) in the kidney...
  65. 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.
  66. ncbi Decreased ENaC expression compensates the increased NCC activity following inactivation of the kidney-specific isoform of WNK1 and prevents hypertension
    Juliette Hadchouel
    Institut National de la Santé et de la Recherche Médicale U970, Paris Cardiovascular Research Center, F 75015 Paris, France
    Proc Natl Acad Sci U S A 107:18109-14. 2010
    Mutations in WNK1 and WNK4 lead to familial hyperkalemic hypertension (FHHt)...
  67. ncbi Angiotensin II diminishes the effect of SGK1 on the WNK4-mediated inhibition of ROMK1 channels
    Peng Yue
    Department of Pharmacology, New York Medical College, Valhalla, New York, USA
    Kidney Int 79:423-31. 2011
    ..However, angiotensin II restored the with-no-lysine kinase-4 (WNK4)-induced inhibition of R1Y337A in the presence of serum-glucocorticoids-induced kinase 1 (SGK1), which reversed the ..
  68. ncbi Estrogen regulation of human with-no-lysine (K) kinase-4 gene expression involves AP-1 transcription factor
    Yuanyuan Zhang
    Department of Medical Genetics, China Medical University, Shenyang, Liaoning, China
    Mol Cell Endocrinol 332:140-8. 2011
    With-no-lysine (K) kinase-4 (WNK4) is a serine/threonine protein kinase and plays a crucial role in the regulation of blood pressure and electrolyte homeostasis...
  69. ncbi Effect of age and affection status on blood pressure, serum potassium and stature in familial hyperkalaemia and hypertension
    Alon Farfel
    Pediatric Endocrinology and Diabetes Unit, Safra Children s Hospital Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Hashomer 52621, Israel
    Nephrol Dial Transplant 26:1547-53. 2011
    The rare autosomal dominant genetic disorder familial hyperkalemia and hypertension which is caused by mutations in WNK4 kinase, is characterized by childhood hyperkalemia and hypercalciuria, and appearance of hypertension in the third to ..
  70. ncbi Genetic disorders of NaCl transport in the distal convoluted tubule
    R Tyler Miller
    Case Western Reserve University, Louis Stokes VAMC, Ramelkamp Center for Research and Education, MetroHealth Medical Center, Cleveland, Ohio, USA
    Nephron Physiol 118:p15-21. 2011
    ..Mutation in two recently identified kinases, WNK1 and WNK4 cause a salt-retaining syndrome through increased apical expression of NaCl cotransporter...
  71. ncbi Acute insulin stimulation induces phosphorylation of the Na-Cl cotransporter in cultured distal mpkDCT cells and mouse kidney
    Eisei Sohara
    Department of Nephrology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
    PLoS ONE 6:e24277. 2011
    ..This insulin-induced phosphorylation of NCC was suppressed in WNK4 and SPAK knockdown cells...
  72. ncbi 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 ..
  73. ncbi Channels, carriers, and pumps in the pathogenesis of sodium-sensitive hypertension
    Giovambattista Capasso
    Department of Nephrology and Research Center for Cardiovascular Diseases, Faculty of Medicine, Second University of Napoli, Napoli, Italy
    Semin Nephrol 25:419-24. 2005
    ..With respect to the Na(+)-Cl(-) cotransporter this may be overactive caused by inactivating mutation of WNK4 as in the Gordon syndrome, although it is the main actor for the maintenance phase of the hypertension found in the ..
  74. ncbi WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis
    Jesse Rinehart
    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 102:16777-82. 2005
    WNK1 and WNK4 [WNK, with no lysine (K)] are serine-threonine kinases that function as molecular switches, eliciting coordinated effects on diverse ion transport pathways to maintain homeostasis during physiological perturbation...
  75. ncbi Analysis of BCL6-interacting proteins by tandem mass spectrometry
    Rodney R Miles
    Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
    Mol Cell Proteomics 4:1898-909. 2005
    ..Many of the novel proteins identified in this study suggest additional functional roles for BCL6 beyond transcriptional repression...
  76. ncbi The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases
    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 391:17-24. 2005
    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...
  77. ncbi Volume sensitivity of cation-Cl- cotransporters is modulated by the interaction of two kinases: Ste20-related proline-alanine-rich kinase and WNK4
    Kenneth B E Gagnon
    Dept of Anesthesiology, Vanderbilt Univ Medical Center, T 4202 Medical Center North, 1161 21st Ave South, Nashville, TN 37232, USA
    Am J Physiol Cell Physiol 290:C134-42. 2006
    ..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)...
  78. ncbi Apical localization of renal K channel was not altered in mutant WNK4 transgenic mice
    Kozue Yamauchi
    Department of Nephrology, Graduate School of Medicine, Tokyo Medical and Dental University, Japan
    Biochem Biophys Res Commun 332:750-5. 2005
    Missense mutations in the WNK4 gene have been postulated to cause pseudohypoaldosteronism type II, an autosomal-dominant disorder characterized by hyperkalemia and hypertension...
  79. ncbi The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics
    Tetsutaro Matayoshi
    Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Japan
    Hypertens Res 27:821-33. 2004
    ..Forty-eight SNPs in 17 genes (ADD1, GNB3, TSC [SLC12A3], MLR [NR3C2], NCX1 [SLC8A1], WNK1, WNK4, AGT, ACE, AT1 [AGTR1], CYP11B2, ADRB1, ADRB2, ADRB3, ADRA1A, ADRA1B, ADRA2A) were genotyped in the 76 patients...
  80. ncbi 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...
  81. 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...
  82. 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...
  83. 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.
  84. 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...
  85. ncbi 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...
  86. 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 ..
  87. 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 ..
  88. 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...
  89. 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 ..
  90. ncbi Antagonistic regulation of ROMK by long and kidney-specific WNK1 isoforms
    Ahmed Lazrak
    Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 8856, USA
    Proc Natl Acad Sci U S A 103:1615-20. 2006
    ..Inhibition of ROMK by long WNK1 was synergistic with, but not dependent on, WNK4. A smaller transcript of WNK1 lacking the N-terminal 1-437 amino acids is expressed highly in the kidney...
  91. ncbi WNK4 regulates the secretory pathway via which TRPV5 is targeted to the plasma membrane
    Yi Jiang
    Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, 1900 University Boulevard, Birmingham, AL 35294 0006, USA
    Biochem Biophys Res Commun 375:225-9. 2008
    ..TRPV5, but not TRPV6, is enhanced by protein kinase WNK4 when expressed in Xenopus laevis oocytes...
  92. ncbi Transcriptional profiling of native inner medullary collecting duct cells from rat kidney
    Panapat Uawithya
    Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
    Physiol Genomics 32:229-53. 2008
    ..WNK1 and WNK4 were also expressed in the IMCD with a relatively high signal intensity, as was protein kinase A (beta-catalytic ..
  93. ncbi Molecular pathogenesis of pseudohypoaldosteronism type II: generation and analysis of a Wnk4(D561A/+) knockin mouse model
    Sung Sen Yang
    Department of Nephrology, Graduate School of Medicine, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo, Tokyo 113 8519, Japan
    Cell Metab 5:331-44. 2007
    WNK1 and WNK4 mutations have been reported to cause pseudohypoaldosteronism type II (PHAII), an autosomal-dominant disorder characterized by hyperkalemia and hypertension...
  94. ncbi Biological cross-talk between WNK1 and the transforming growth factor beta-Smad signaling pathway
    Byung Hoon Lee
    Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9041, USA
    J Biol Chem 282:17985-96. 2007
    ..Both WNK1 and WNK4 directly bind to and phosphorylate Smad2...
  95. 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...
  96. ncbi WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo
    Aaron M Ring
    Departments of Genetics, Medicine, and Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 104:4020-4. 2007
    ..Previous work has shown that mutations in WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension with hyperkalemia, due to altered ..
  97. ncbi WNK1 and WNK4 modulate CFTR activity
    Chao Ling Yang
    Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, OR 97239, USA
    Biochem Biophys Res Commun 353:535-40. 2007
    ..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 in ..
  98. ncbi WNK kinases, renal ion transport and hypertension
    Pedro San-Cristobal
    Molecular Physiology Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán and Instituto de Investigaciones Biomédicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
    Am J Nephrol 28:860-70. 2008
    ..The uncovered genes causing PHAII encode for serine/threonine kinases known as WNK1 and WNK4. Physiological and biochemical studies have revealed that WNK1 and WNK4 modulate the activity of several transport ..
  99. ncbi Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule
    Maria D Lalioti
    Department of Genetics, Howard Hughes Medical, Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Genet 38:1124-32. 2006
    ..Mutations in the gene encoding the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and hyperkalemia...
  100. ncbi Overexpression of human WNK1 increases paracellular chloride permeability and phosphorylation of claudin-4 in MDCKII cells
    Akihito Ohta
    Department of Nephrology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Biochem Biophys Res Commun 349:804-8. 2006
    ..by hypertension, hyperkalemia, and hyperchloremic acidosis, is reportedly due to mutations in WNK1 and WNK4 kinase genes. However, the pathogenesis of the disease remains unknown...
  101. ncbi A single binding motif is required for SPAK activation of the Na-K-2Cl cotransporter
    Kenneth B E Gagnon
    Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 2520, USA
    Cell Physiol Biochem 20:131-42. 2007
    ..phosphorylates and activates NKCC1 (Na-K-2Cl cotransporter) in the presence of another serine/threonine kinase WNK4 (With No lysine (K))...

Research Grants75

  1. Function of STE20 Related Protein Kinases
    Melanie Cobb; Fiscal Year: 2007
    ..Lifton et al. found that mutations in either WNK1 or WNK4 causes pseudohypoaldosteronism type II, a heritable form of hypertension...
  2. REGULATION OF THE SODIUM CHLORIDE COTRANSPORTER
    Robert Hoover; Fiscal Year: 2007
    ..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 ..
  3. Sodium Chloride Cotransporter Regulation by WNK Kinase
    Hui Cai; Fiscal Year: 2006
    ..Mutations in WNK1 and WNK4 kinases are found to cause pseudohypoaldosteronism type II (PHA II), also referred to as Gordon syndrome...
  4. Coordination of Renal K and Na Transport by Vesicle Traffic
    James B Wade; Fiscal Year: 2010
    ..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? ..
  5. The Function of Claudin-7 in Renal Epithelial Cells
    Yan Hua Chen; Fiscal Year: 2009
    ..Mutations in WNK4 kinase have been linked to hypertension in pseudohypoaldosteronism type II (PHAII)...
  6. The Function of Claudin-7 in Renal Epithelial Cells
    Yan Hua Chen; Fiscal Year: 2010
    ..Mutations in WNK4 kinase have been linked to hypertension in pseudohypoaldosteronism type II (PHAII)...
  7. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2010
    ..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...
  8. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie Cobb; Fiscal Year: 2009
    ..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...
  9. Genetic determinants of urine lithogenicity
    JOHN LIESKE; Fiscal Year: 2009
    ..candidate gene associations (vitamin D receptor, soluble adenylate cyclase, intracellular protease with no lysine WNK4, chloride channel CLCN5, calcium sensing receptor, urinary prothrombin fragment 1, urate anion transporter 1, ..
  10. Genetic determinants of urine lithogenicity
    JOHN LIESKE; Fiscal Year: 2009
    ..candidate gene associations (vitamin D receptor, soluble adenylate cyclase, intracellular protease with no lysine WNK4, chloride channel CLCN5, calcium sensing receptor, urinary prothrombin fragment 1, urate anion transporter 1, ..
  11. Genetic determinants of urine lithogenicity
    John C Lieske; Fiscal Year: 2010
    ..candidate gene associations (vitamin D receptor, soluble adenylate cyclase, intracellular protease with no lysine WNK4, chloride channel CLCN5, calcium sensing receptor, urinary prothrombin fragment 1, urate anion transporter 1, ..
  12. 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)...
  13. Regulation of thiazide-sensitive NaCl transport
    David Ellison; Fiscal Year: 2007
    ..We show preliminary data indicating that WNK kinases regulate thiazide-sensitive Na-CI cotransporter activity. WNK4 suppresses thiazide-sensitive Na-CI cotransporter activity by more than 80%...
  14. Mechanisms of Hormonal Regulation of the Sodium Chloride Cotransporter
    Robert S Hoover; Fiscal Year: 2010
    ..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 ..
  15. Membrane Trafficking of Renal Potassium Channel
    Chou Long Huang; Fiscal Year: 2009
    ..Mutations of WNK1 and WNK4 cause PHA II...
  16. Mechanisms of Regulation of Anion Exchanger SLC26A6
    Hatim Hassan; Fiscal Year: 2007
    ..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. KINASES IN ION COTRANSPORTER FUNCTION
    Eric J Delpire; Fiscal Year: 2010
    ..Together with WNK4, a kinase that is associated with human hypertension, the stress kinases modulate the activity of the ..
  18. Molecular Physiology of the renal Na-Cl cotransporter
    Gerardo Gamba; Fiscal Year: 2007
    ..for ion translocation, the diuretic binding affinity and the response to regulation by cell volume and by WNK4 kinase...
  19. KINASES IN ION COTRANSPORTER FUNCTION
    Eric Delpire; Fiscal Year: 2007
    ..Together with WNK4, a kinase that is associated with human hypertension, the stress kinases modulate the activity of the ..
  20. Coordination of Renal K and Na Transport by Vesicle Traffic
    James Wade; Fiscal Year: 2007
    ..Recent work has identified a role for the "With No Lysine" kinases (WNK4, WNK1, and KD-WNK1) in regulating the surface expression of the K channel, ROMK...
  21. Regulation of thiazide-sensitive NaCl transport
    David H Ellison; Fiscal Year: 2010
    ..WNK1, WNK3, and WNK4 have distinct properties to stimulate or inhibit salt transport, effects that can be modified based on ..
  22. RENAL POTASSIUM TRANSPORT IN PHYSIOLOGY AND DISEASES
    Chou Long Huang; Fiscal Year: 2001
    ..The structural and functional constraints conferred by Bartter's mutation will be examined by screening libraries of ROMK constructed by saturation mutagenesis in a potassium uptake-defective yeast strains. ..
  23. Membrane Trafficking of Renal Potassium Channel
    Chou Long Huang; Fiscal Year: 2010
    ..Mutations of WNK1 and WNK4 cause PHA II...
  24. Regulation of renal calcium transport
    Chou Long Huang; Fiscal Year: 2010
    ..Increase in urinary calcium excretion is a major cause for kidney stone formation. Our studies will help to understand why calcium stone forms and to design treatment for the disease. ..
  25. 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. ..
  26. Membrane Trafficking of Renal Potassium Channel
    Chou Long Huang; Fiscal Year: 2006
    ..Biochemical binding assay and patch-clamp recording will be performed to examine this hypothesis. ..
  27. Interplay of Renal Ca and Na Transport Pathways
    Ji Bin Peng; Fiscal Year: 2010
    ..is prominently localized in the apical membrane of the late segment of the distal convoluted tubule, where NCC and WNK4 are also expressed. WNK4 enhances TRPVS-mediated Ca transport in striking contrast to its inhibitory effect on NCC...
  28. Interplay of Renal Ca and Na Transport Pathways
    Ji Bin Peng; Fiscal Year: 2009
    ..is prominently localized in the apical membrane of the late segment of the distal convoluted tubule, where NCC and WNK4 are also expressed. WNK4 enhances TRPVS-mediated Ca transport in striking contrast to its inhibitory effect on NCC...
  29. Interplay of Renal Ca and Na Transport Pathways
    Ji Bin Peng; Fiscal Year: 2010
    ..is prominently localized in the apical membrane of the late segment of the distal convoluted tubule, where NCC and WNK4 are also expressed. WNK4 enhances TRPVS-mediated Ca transport in striking contrast to its inhibitory effect on NCC...
  30. Interplay of Renal Ca and Na Transport Pathways
    Ji Bin Peng; Fiscal Year: 2009
    ..is prominently localized in the apical membrane of the late segment of the distal convoluted tubule, where NCC and WNK4 are also expressed. WNK4 enhances TRPVS-mediated Ca transport in striking contrast to its inhibitory effect on NCC...