2007
An SGK1 site in WNK4 regulates Na+ channel and K+ channel activity and has implications for aldosterone signaling and K+ homeostasis
Ring AM, Leng Q, Rinehart J, Wilson FH, Kahle KT, Hebert SC, Lifton RP. An SGK1 site in WNK4 regulates Na+ channel and K+ channel activity and has implications for aldosterone signaling and K+ homeostasis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 4025-4029. PMID: 17360471, PMCID: PMC1803763, DOI: 10.1073/pnas.0611728104.Peer-Reviewed Original ResearchConceptsIntravascular volume depletionNa-Cl cotransporterAldosterone signalingPseudohypoaldosteronism type IIVolume depletionPhysiologic responsesNaCl reabsorptionPHAII-mutant WNK4Steroid hormone aldosteroneRenal outer medullaryRenal NaCl reabsorptionFunctional stateWNK4 mutationsROMK activityHormone aldosteroneOuter medullaryHyperkalemiaSecretionKidneyWild-type WNK4ReabsorptionAldosteroneChannel activityChannel ENaCWNK4
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
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 mutation