2007
WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo
Ring AM, Cheng SX, Leng Q, Kahle KT, Rinehart J, Lalioti MD, Volkman HM, Wilson FH, Hebert SC, Lifton RP. WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 4020-4024. PMID: 17360470, PMCID: PMC1805455, DOI: 10.1073/pnas.0611727104.Peer-Reviewed Original ResearchConceptsPseudohypoaldosteronism type IIDistal nephronPHAII-mutant WNK4Wild-type littermatesNa-Cl cotransporterAldosterone systemIntravascular volumeDistal colonSodium balanceElectrolyte homeostasisColonic epitheliumMajor mediatorDiverse mediatorsAltered activityENaC betaWNK4's inhibitionKinase activityIntact C-terminusPHAII-causing mutationsMiceWNK4MediatorsDownstream targetsWNK4 kinase activityENaC
2006
WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1)
Leng Q, Kahle KT, Rinehart J, MacGregor GG, Wilson FH, Canessa CM, Lifton RP, Hebert SC. WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1). The Journal Of Physiology 2006, 571: 275-286. PMID: 16357011, PMCID: PMC1796803, DOI: 10.1113/jphysiol.2005.102202.Peer-Reviewed Original ResearchConceptsDistal convoluted tubuleInhibition of ROMK1KCNQ1/KCNE1Renal NaCl reabsorptionEpithelial sodium channelAmiloride-sensitive currentDistal nephronVivo effectsConvoluted tubulesKinase-dependent activationQT syndromeNCC activityNaCl reabsorptionNephron segmentsDuct principal cellsHereditary hypertensionSodium channelsPrincipal cellsII cellsRenal NaClSurface expressionXenopus laevis oocytesHypertensionHomeostatic systemDisease
2004
A Cluster of Metabolic Defects Caused by Mutation in a Mitochondrial tRNA
Wilson FH, Hariri A, Farhi A, Zhao H, Petersen KF, Toka HR, Nelson-Williams C, Raja KM, Kashgarian M, Shulman GI, Scheinman SJ, Lifton RP. A Cluster of Metabolic Defects Caused by Mutation in a Mitochondrial tRNA. Science 2004, 306: 1190-1194. PMID: 15498972, PMCID: PMC3033655, DOI: 10.1126/science.1102521.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgingAnticodonBody Mass IndexCluster AnalysisCytidineExtrachromosomal InheritanceFemaleHumansHypercholesterolemiaHypertensionMagnesiumMaleMetabolic SyndromeMiddle AgedMitochondriaMitochondria, MuscleMuscle Fibers, SkeletalMutationPedigreePhenotypeRNARNA, MitochondrialRNA, Transfer, IleSyndromeThymidineUridineParacellular Cl- permeability is regulated by WNK4 kinase: Insight into normal physiology and hypertension
Kahle KT, MacGregor GG, Wilson FH, Van Hoek AN, Brown D, Ardito T, Kashgarian M, Giebisch G, Hebert SC, Boulpaep EL, Lifton RP. Paracellular Cl- permeability is regulated by WNK4 kinase: Insight into normal physiology and hypertension. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 14877-14882. PMID: 15465913, PMCID: PMC522037, DOI: 10.1073/pnas.0406172101.Peer-Reviewed Original ResearchConceptsPseudohypoaldosteronism type IIPHAII-mutant WNK4Paracellular fluxPotent antihypertensive agentTight junction proteinsTight junctionsAntihypertensive agentsParacellular ion fluxPharmacologic propertiesTight junction structureTranscellular transportersWild-type WNK4Normal physiologyHypertensionTransepithelial resistanceWNK signalingKidney epitheliumTight junction formationParacellular pathwayWNK4Effect of WNK4EpitheliumType IIWNK4 kinaseHomeostasis
2003
WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse Cl−-transporting epithelia
Choate KA, Kahle KT, Wilson FH, Nelson-Williams C, Lifton RP. WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse Cl−-transporting epithelia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 663-668. PMID: 12522152, PMCID: PMC141053, DOI: 10.1073/pnas.242728499.Peer-Reviewed Original ResearchConceptsPseudohypoaldosteronism type IIPancreatic ductCl fluxRenal tubular acidosisSweat ductsAutosomal dominant disorderBile ductBiliary ductsTubular acidosisExtrarenal tissuesDistal nephronCl reabsorptionEsophageal epitheliumCystic fibrosisWNK4 expressionColonic cryptsEpitheliumDominant disorderSelective modulationHypertensionHyperkalemiaBasal layerGallbladderDuctKidneyMolecular pathogenesis of inherited hypertension with hyperkalemia: The Na–Cl cotransporter is inhibited by wild-type but not mutant WNK4
Wilson FH, Kahle KT, Sabath E, Lalioti MD, Rapson AK, Hoover RS, Hebert SC, Gamba G, Lifton RP. Molecular pathogenesis of inherited hypertension with hyperkalemia: The Na–Cl cotransporter is inhibited by wild-type but not mutant WNK4. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 680-684. PMID: 12515852, PMCID: PMC141056, DOI: 10.1073/pnas.242735399.Peer-Reviewed Original ResearchConceptsNa-Cl cotransporterPseudohypoaldosteronism type IIMutant WNK4Molecular pathogenesisThiazide-sensitive Na-Cl cotransporterSerine-threonine kinases WNK1Forms of hypertensionMembrane expressionMissense mutationsMetabolic acidosisT cellsDistal nephronPHAII phenotypesHypertensionNa influxHEK 293T cellsSurface expressionWNK signalingHyperkalemiaFunction mutationsPathogenesisCotransporterWNK4
2002
Salt and blood pressure: new insight from human genetic studies.
Lifton RP, Wilson FH, Choate KA, Geller DS. Salt and blood pressure: new insight from human genetic studies. Cold Spring Harbor Symposia On Quantitative Biology 2002, 67: 445-50. PMID: 12858570, DOI: 10.1101/sqb.2002.67.445.Books
2001
Human Hypertension Caused by Mutations in WNK Kinases
Wilson F, Disse-Nicodème S, Choate K, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford D, Lipkin G, Achard J, Feely M, Dussol B, Berland Y, Unwin R, Mayan H, Simon D, Farfel Z, Jeunemaitre X, Lifton R. Human Hypertension Caused by Mutations in WNK Kinases. Science 2001, 293: 1107-1112. PMID: 11498583, DOI: 10.1126/science.1062844.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBase SequenceChromosome MappingChromosomes, Human, Pair 12Chromosomes, Human, Pair 17CytoplasmFemaleGene Expression Regulation, EnzymologicGenetic LinkageHumansHypertensionIntercellular JunctionsIntracellular Signaling Peptides and ProteinsIntronsKidney Tubules, CollectingKidney Tubules, DistalMaleMembrane ProteinsMicroscopy, FluorescenceMinor Histocompatibility AntigensMolecular Sequence DataMutationMutation, MissensePedigreePhosphoproteinsProtein Serine-Threonine KinasesPseudohypoaldosteronismSequence DeletionSignal TransductionWNK Lysine-Deficient Protein Kinase 1Zonula Occludens-1 ProteinConceptsMajor public health problemPublic health problemRenal salt reabsorptionAntihypertensive drugsHuman hypertensionUnknown causeDistal nephronKidney segmentsPseudohypoaldosteronism type IIHealth problemsSalt reabsorptionHypertensionWNK1 expressionNew targetsWNK kinasesTight junctionsType IISerine-threonine kinaseIntronic deletionWNK4WNK familyMutationsWNK1KinaseExcretion