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 reabsorptionTransportersHomeostasisRegulation of diverse ion transport pathways by WNK4 kinase: a novel molecular switch
Kahle KT, Wilson FH, Lifton RP. Regulation of diverse ion transport pathways by WNK4 kinase: a novel molecular switch. Trends In Endocrinology And Metabolism 2005, 16: 98-103. PMID: 15808806, DOI: 10.1016/j.tem.2005.02.012.Peer-Reviewed Original ResearchConceptsWNK kinasesSerine-threonine kinaseNovel molecular switchSubstitution of cysteinePhysiological regulatory pathwaysRecent physiological workMolecular genetic studiesCatalytic domainSubdomain IIRegulatory pathwaysIon flux pathwaysMolecular switchWNK4 kinaseKinasePhysiological workBasolateral membranePathwayIon transport pathwaysTransport pathwaysWNK4Electrolyte homeostasisProminent roleSyndrome of hypertensionWNK1Key component
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 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 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