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
2004
WNK kinases: molecular regulators of integrated epithelial ion transport
Kahle KT, Wilson FH, Lalioti M, Toka H, Qin H, Lifton RP. WNK kinases: molecular regulators of integrated epithelial ion transport. Current Opinion In Nephrology & Hypertension 2004, 13: 557-562. PMID: 15300163, DOI: 10.1097/00041552-200409000-00012.Peer-Reviewed Original ResearchMeSH KeywordsEpitheliumHumansIon TransportKidneyPoint MutationProtein Serine-Threonine KinasesPseudohypoaldosteronismSignal TransductionConceptsPseudohypoaldosteronism type IIWNK kinasesPotassium ion channelsChloride ion fluxIon channelsSerine-threonine kinaseCoordinated regulationDiverse epitheliaMolecular regulatorsMolecular switchKinasePotassium ion secretionDynamic regulatorGeneral roleDisease physiologyIon fluxIntegrated regulationElectrolyte homeostasisEpithelial ion transportEpithelial transportersEssential roleWNK4HomeostasisFlux pathwaysMutations
2003
WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion
Kahle KT, Wilson FH, Leng Q, Lalioti MD, O'Connell AD, Dong K, Rapson AK, MacGregor GG, Giebisch G, Hebert SC, Lifton RP. WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion. Nature Genetics 2003, 35: 372-376. PMID: 14608358, DOI: 10.1038/ng1271.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsClathrinEndocytosisGreen Fluorescent ProteinsIon TransportKidneyLuminescent ProteinsMicePotassiumPotassium ChannelsPotassium Channels, Inwardly RectifyingProtein Serine-Threonine KinasesPseudohypoaldosteronismRatsReceptors, DrugSodium ChlorideSodium Chloride SymportersSolute Carrier Family 12, Member 3SymportersXenopus laevisConceptsDiverse ion transportersClathrin-dependent endocytosisSerine-threonine kinase WNK4WNK4 kinase activityRenal Na-Cl cotransporterDiverse physiologic processesRenal NaClWild-type WNK4Positional cloningMultifunctional regulatorXenopus laevis oocytesInhibition of ROMKIon transportersKinase activityGenetic analysisSystems biologyMolecular switchNa-Cl cotransporterWNK4's inhibitionLaevis oocytesChannel ROMKWNK4Renal NaCl reabsorptionMutationsSame mutation
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