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Science 10 August 2001:
Vol. 293. no. 5532, pp. 1107 - 1112
DOI: 10.1126/science.1062844
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Research Articles

Human Hypertension Caused by Mutations in WNK Kinases

Frederick H. Wilson,1 Sandra Disse-Nicodème,2* Keith A. Choate,1* Kazuhiko Ishikawa,1* Carol Nelson-Williams,1 Isabelle Desitter,2 Murat Gunel,1 David V. Milford,3 Graham W. Lipkin,4 Jean-Michel Achard,5 Morgan P. Feely,6 Bertrand Dussol,7 Yvon Berland,7 Robert J. Unwin,8 Haim Mayan,9 David B. Simon,1 Zvi Farfel,9 Xavier Jeunemaitre,2 Richard P. Lifton1dagger

Hypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein. Both proteins localize to the distal nephron, a kidney segment involved in salt, K+, and pH homeostasis. WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs.

1 Howard Hughes Medical Institute; Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06510 USA.
2 INSERM U36, Collège de France. 11, Place Marcellin Berthelot. 75005 Paris, France.
3 Department of Nephrology, Birmingham Children's Hospital, Birmingham B4 6NH, UK.
4 Department of Nephrology, Queen Elizabeth Hospital, Birmingham B15 2TH, UK.
5 Service de Néphrologie, Hopital d'Amiens-Sud, Amiens, France.
6 Unit of Molecular Vascular Medicine, The General Infirmary, Leeds, UK.
7 Service de Néphrologie et Hémodialyse, Hopital Sainte Marguerite, Marseille, France.
8 Departments of Nephrology and Physiology, University College London, London W1W 7EY, UK.
9 Department of Medicine E' and Laboratory of Biochemical Pharmacology, Sheba Medical Center, Tel Aviv University School of Medicine, Tel Hashomer 52621, Israel.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: richard.lifton{at}yale.edu

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Exploring the role of galectin 3 in kidney function: a genetic approach.
M. Bichara, A. Attmane-Elakeb, D. Brown, M. Essig, Z. Karim, M. Muffat-Joly, L. Micheli, I. Eude-Le Parco, F. Cluzeaud, M. Peuchmaur, et al. (2006)
Glycobiology 16, 36-45
   Abstract »    Full Text »    PDF »
Tight junction biology and kidney dysfunction.
D. B. N. Lee, E. Huang, and H. J. Ward (2006)
Am J Physiol Renal Physiol 290, F20-F34
   Abstract »    Full Text »    PDF »
Familial Hyperkalemic Hypertension.
J. Hadchouel, C. Delaloy, S. Faure, J.-M. Achard, and X. Jeunemaitre (2006)
J. Am. Soc. Nephrol. 17, 208-217
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Volume sensitivity of cation-Cl- cotransporters is modulated by the interaction of two kinases: Ste20-related proline-alanine-rich kinase and WNK4.
K. B. E. Gagnon, R. England, and E. Delpire (2006)
Am J Physiol Cell Physiol 290, C134-C142
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WNK1 Regulates Phosphorylation of Cation-Chloride-coupled Cotransporters via the STE20-related Kinases, SPAK and OSR1.
T. Moriguchi, S. Urushiyama, N. Hisamoto, S.-i. Iemura, S. Uchida, T. Natsume, K. Matsumoto, and H. Shibuya (2005)
J. Biol. Chem. 280, 42685-42693
   Abstract »    Full Text »    PDF »
Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells.
C. Le Moellic, S. Boulkroun, D. Gonzalez-Nunez, I. Dublineau, F. Cluzeaud, M. Fay, M. Blot-Chabaud, and N. Farman (2005)
Am J Physiol Cell Physiol 289, C1513-C1521
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Association of Blood Pressure With Genetic Variation in WNK Kinases in a White European Population.
H. Zhang and J. A. Staessen (2005)
Circulation 112, 3371-3372
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Association of WNK1 Gene Polymorphisms and Haplotypes With Ambulatory Blood Pressure in the General Population.
M. D. Tobin, S. M. Raleigh, S. Newhouse, P. Braund, C. Bodycote, J. Ogleby, D. Cross, J. Gracey, S. Hayes, T. Smith, et al. (2005)
Circulation 112, 3423-3429
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WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis.
J. Rinehart, K. T. Kahle, P. de los Heros, N. Vazquez, P. Meade, F. H. Wilson, S. C. Hebert, I. Gimenez, G. Gamba, and R. P. Lifton (2005)
PNAS 102, 16777-16782
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WNK3 modulates transport of Cl- in and out of cells: Implications for control of cell volume and neuronal excitability.
K. T. Kahle, J. Rinehart, P. de los Heros, A. Louvi, P. Meade, N. Vazquez, S. C. Hebert, G. Gamba, I. Gimenez, and R. P. Lifton (2005)
PNAS 102, 16783-16788
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A Phosphorylation-dependent Export Structure in ROMK (Kir 1.1) Channel Overrides an Endoplasmic Reticulum Localization Signal.
D. Yoo, L. Fang, A. Mason, B.-Y. Kim, and P. A. Welling (2005)
J. Biol. Chem. 280, 35281-35289
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