2005
WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis
Rinehart J, Kahle KT, de los Heros P, Vazquez N, Meade P, Wilson FH, Hebert SC, Gimenez I, Gamba G, Lifton RP. WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 16777-16782. PMID: 16275913, PMCID: PMC1283841, DOI: 10.1073/pnas.0508303102.Peer-Reviewed Original ResearchConceptsEffects of WNK3Kinase-inactive stateSerine-threonine kinaseWNK kinase familyActivation of NKCC2Kinase familyPositive regulatorThr-189Potent inhibitorPlasma membraneRelated membersThr-184Coexpression studiesMolecular switchNKCC2 phosphorylationFunction mutationsNormal blood pressure homeostasisWNK3Intercellular junctionsBlood pressure homeostasisRenal epitheliumPotent activatorRenal NaCl reabsorptionTransportersHomeostasis
2004
Paracellular 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 kinaseHomeostasisWNK 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 ResearchConceptsPseudohypoaldosteronism 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 pathwaysMutationsWNK4 regulates apical and basolateral Cl– flux in extrarenal epithelia
Kahle KT, Gimenez I, Hassan H, Wilson FH, Wong RD, Forbush B, Aronson PS, Lifton RP. WNK4 regulates apical and basolateral Cl– flux in extrarenal epithelia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 2064-2069. PMID: 14769928, PMCID: PMC357052, DOI: 10.1073/pnas.0308434100.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCarrier ProteinsCell PolarityChloridesEpitheliumHumansImmunohistochemistryIon TransportKidneyMembrane ProteinsMembrane Transport ProteinsMiceOocytesProtein Serine-Threonine KinasesRNA, MessengerSodium-Potassium-Chloride SymportersSolute Carrier Family 12, Member 2Sulfate TransportersXenopus laevisConceptsCl fluxBlood-brain barrierUnrelated ion channelsActivity of mediatorsWNK4 mRNABile ductPancreatic ductExtrarenal expressionExtrarenal tissuesCl(-) handlingPseudohypoaldosteronism type IIChannel ROMKNaCl reabsorptionSerine-threonine kinase WNK4Specialized endotheliumExchanger SLC26A6NaCl cotransporterWNK4 effectsColonic cryptsEpitheliumVariable inhibitionSweat ductsTight junctionsKidneyElectrolyte flux
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
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
1999
Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter
Race J, Makhlouf F, Logue P, Wilson F, Dunham P, Holtzman E. Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter. American Journal Of Physiology 1999, 277: c1210-c1219. PMID: 10600773, DOI: 10.1152/ajpcell.1999.277.6.c1210.Peer-Reviewed Original ResearchMeSH KeywordsBiological TransportCarrier ProteinsCell LineChlorineChromosome MappingCloning, MolecularDNA PrimersEthylmaleimideGene ExpressionHumansKidneyMolecular Sequence DataOsmosisPhylogenyPlacentaPotassiumProtein Structure, TertiarySequence Homology, Amino AcidSulfhydryl ReagentsSymportersTransfectionConceptsCation-chloride cotransporter familyK-Cl cotransporterNa-Cl cotransporterTransmembrane domain 5Large extracellular loopStimulation of cotransportAmino acid levelsHydropathy analysisDeduced proteinHuman embryonic kidneyNa-K-Cl cotransporterTransmembrane domainMolecular cloningK-Cl cotransportFunctional characterizationCotransporter familyExtracellular loopEmbryonic kidneyDomain 5Amino acidsKCC3Human placentaAcid levelsSkeletal muscleCotransporter