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A new locus on chromosome 12p13.3 for pseudohypoaldosteronism type II, an autosomal dominant form of hypertension
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Three novel missense mutations of WNK4, a kinase mutated in inherited hypertension, in Japanese hypertensives: Implication of clinical phenotypes
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Kamide K, Takiuchi S, Tanaka C, et al. Three novel missense mutations of WNK4, a kinase mutated in inherited hypertension, in Japanese hypertensives: implication of clinical phenotypes. Am J Hypertens 2004; 17:446-449.
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Kamide, K.1
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WNK1, a novel mammalian serine/ threonine protein kinase lacking the catalytic lysine in subdomain II
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Xu B, English JM, Wilsbacher JL, et al. WNK1, a novel mammalian serine/ threonine protein kinase lacking the catalytic lysine in subdomain II. J Biol Chem 2000; 275:16795-16801.
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Regulation of WNK1 by an autoinhibitory domain and autophosphorylation
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Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter
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Simon DB, Nelson-Williams C, Bia MJ, et al. Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet 1996; 12:24-30.
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Molecular pathogenesis of inherited hypertension with hyperkalemia; the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4
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Wilson FH, Kahle KT, Sabath E, et al. Molecular pathogenesis of inherited hypertension with hyperkalemia; the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4. Proc Natl Acad Sci U S A 2003; 100:680-684. This study demonstrates the inhibition of NCCT by WNK4 and that inhibition is kinase-dependent and results from the loss of NCCT from the cell surface. Both PHAII mutations tested lose inhibitory activity.
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Proc Natl Acad Sci U S A
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WNK kinases regulate thiazide-sensitive Na-Cl cotransport
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Yang CL, Angell J, Mitchell R, et al. WNK kinases regulate thiazide-sensitive Na-Cl cotransport. J Clin Invest 2003; 111:1039-1045. This study demonstrates the inhibition of NCCT by WNK4, and suggests that WNK1 inhibits WNK4.
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+ secretion
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+ secretion. Nat Genet 2003; 35:372-376. This study established that WNK4 inhibits ROMK activity and that PHAII mutations show increased inhibition. It established that WNK4 can independently regulate NCCT and ROMK, explaining the PHAII phenotype and establishing WNK4 as a molecular switch.
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Nat Genet
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Kahle, K.T.1
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Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins
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Yamauchi K, Rai T, Kobayashi K, et al. Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins. Proc Natl Acad Sci U S A 2004; 101:4690-4694. This study provides evidence for the role of WNK4 in the regulation of paracellular chloride ion flux.
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Yamauchi, K.1
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Abstract. American Society of Nephrology, Philadelphia, USA, in press.
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Kahle KT, MacGregor GG, Hebert SC, et al. WNK4 regulates paracellular CI permeability [Abstract]. American Society of Nephrology, Philadelphia, USA, 2004; in press.
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WNK4 Regulates Paracellular CI Permeability
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Kahle, K.T.1
MacGregor, G.G.2
Hebert, S.C.3
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19
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WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse CI-transporting epithelia
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Choate KA, Kahle KT, Wilson FH, et al. WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse CI-transporting epithelia. Proc Natl Acad Sci U S A 2003; 100:663-668.
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- flux in extrarenal epithelia. Proc Natl Acad Sci U S A 2004; 101:2064-2069. This study demonstrates the presence of WNK4 in polarized epithelia in diverse tissues involved in chloride ion flux.
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Proc Natl Acad Sci U S A
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Kahle, K.T.1
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Comparison of WNK4 and WNK1 kinase and inhibiting activities
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Wang Z, Yang CL, Ellison DH. Comparison of WNK4 and WNK1 kinase and inhibiting activities. Biochem Biophys Res Commun 2004; 317:939-944.
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WNK1, a gene within a novel blood pressure control pathway, tissue-specifically generates radically different isoforms with and without a kinase domain
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O'Reilly M, Marshall E, Speirs HJ, et al. WNK1, a gene within a novel blood pressure control pathway, tissue-specifically generates radically different isoforms with and without a kinase domain. J Am Soc Nephrol 2003; 14:2447-2456. The demonstration of a kidney-specific WNK1 isoform without a kinase domain, and its expression in the DCT of the nephron.
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J Am Soc Nephrol
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O'Reilly, M.1
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Multiple promoters in the WNK1 gene: One controls expression of a kidney-specific kinase-defective isoform
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Delaloy C, Lu J, Houot AM, et al. Multiple promoters in the WNK1 gene: one controls expression of a kidney-specific kinase-defective isoform. Mol Cell Biol 2003; 23:9208-9221. The demonstration of multiple transcription start sites and WNK1 isoforms in the kidney, as well as a conserved enhancer element conserved among genes expressed in DCT.
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Mol Cell Biol
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WNK1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention
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Zambrowicz BP, Abuin A, Ramirez-Solis R, et al. WNK1 kinase deficiency lowers blood pressure in mice: a gene-trap screen to identify potential targets for therapeutic intervention. Proc Natl Acad Sci U S A 2003; 100:14109-14114. The targeted disruption of WNK1 is homozygous lethal; however, the heterozygous knockout mouse shows reduced blood pressure.
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Proc Natl Acad Sci U S A
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Zambrowicz, B.P.1
Abuin, A.2
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25
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1542314814
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WNK1, the kinase mutated in an inherited high-blood-pressure syndrome, is a novel PKB (protein kinase B)/Akt substrate
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Vitari AC, Deak M, Collins BJ, et al. WNK1, the kinase mutated in an inherited high-blood-pressure syndrome, is a novel PKB (protein kinase B)/Akt substrate. Biochem J 2004; 378:257-268. This interesting finding raises the possibility that insulin signaling may regulate WNK activity.
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Biochem J
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Vitari, A.C.1
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Xu BE, Stippec S, Lenertz L, et al. WNK1 activates ERK5 by a MEKK2/3-dependent mechanism. J Biol Chem 2004; 279:7826-7831. This study puts WNK1 upstream of ERK5 signaling.
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Xu, B.E.1
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