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
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 mutationMolecular 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
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