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
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 kinaseHomeostasis
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