2004
WNK4 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
2001
Modulation of Ion Transport by Direct Targeting of Protein Phosphatase Type 1 to the Na-K-Cl Cotransporter*
Darman R, Flemmer A, Forbush B. Modulation of Ion Transport by Direct Targeting of Protein Phosphatase Type 1 to the Na-K-Cl Cotransporter*. Journal Of Biological Chemistry 2001, 276: 34359-34362. PMID: 11466303, DOI: 10.1074/jbc.c100368200.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1Substrate proteinsNa-K-Cl cotransporterProtein phosphatase type 1Phosphatase type 1Intracellular chloride regulationPhosphatase specificityRegulatory phosphorylationPhosphatase 1Catalytic subunitMotif bindsSubunit bindsN-terminusPP1cMajor proteinsDirect bindingDirect interactionChloride regulationProteinGeneral mechanismDirect targetingMutantsMotifSubunitsBinds
2000
Basolateral K-Cl Cotransporter Regulates Colonic Potassium Absorption in Potassium Depletion*
Sangan P, Brill S, Sangan S, Forbush B, Binder H. Basolateral K-Cl Cotransporter Regulates Colonic Potassium Absorption in Potassium Depletion*. Journal Of Biological Chemistry 2000, 275: 30813-30816. PMID: 10878016, DOI: 10.1074/jbc.m003931200.Peer-Reviewed Original ResearchConceptsK-Cl cotransporterMembrane HK-Cl cotransportActive potassium absorptionProtein expressionBasolateral membranePotassium absorptionK-ATPaseNorthern blot analysisKCC1 mRNACoordinated regulationAlpha-subunit mRNABeta-subunit mRNAMRNA abundanceBlot analysisMRNAExpressionProteinMembraneCotransporterDepletionRat distal colonCDNAKCC1The Na-K-Cl Cotransporter of Secretory Epithelia
Haas M, Forbush B. The Na-K-Cl Cotransporter of Secretory Epithelia. Annual Review Of Physiology 2000, 62: 515-534. PMID: 10845101, DOI: 10.1146/annurev.physiol.62.1.515.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsEpithelial CellsHumansMembrane ProteinsSodium-Potassium-Chloride SymportersConceptsNa-K-ClNa-K-Cl cotransporterRegulation of NKCC1Secretory epitheliaNa-K-Cl cotransporter isoformsK-Cl cotransporter isoformsApical Cl- channelsNa-Cl cotransporterNon-epithelial cellsNKCC1 regulationCl- channelsBasolateral membraneCotransporter proteinFluid secretionNKCC isoformsNKCC1Ascending limbHenle's loopEpithelial cellsMacula densaIon transport proteinsTransport NaEpitheliaCotransporterCell volume
1999
Functional interaction of the K-Cl cotransporter (KCC1) with the Na-K-Cl cotransporter in HEK-293 cells
Gillen C, Forbush B. Functional interaction of the K-Cl cotransporter (KCC1) with the Na-K-Cl cotransporter in HEK-293 cells. American Journal Of Physiology 1999, 276: c328-c336. PMID: 9950760, DOI: 10.1152/ajpcell.1999.276.2.c328.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-Cl cotransport activityNa-K-ClK-Cl cotransportHEK-293 cellsCotransport activityK-ClHEK-293Activation of Na-K-Cl cotransportCell swellingK-Cl cotransport activityHypotonic cell swellingIntracellular Cl- concentrationFunctional interactionsKCC1External KCotransporterIon-transporting epitheliaCell linesN-ethylmaleimidePhysiological rangeCellsInvestigate functional interactionsCross-talkPretreatment
1998
Mutagenic Mapping of the Na-K-Cl Cotransporter for Domains Involved in Ion Transport and Bumetanide Binding
Isenring P, Jacoby S, Chang J, Forbush B. Mutagenic Mapping of the Na-K-Cl Cotransporter for Domains Involved in Ion Transport and Bumetanide Binding. The Journal Of General Physiology 1998, 112: 549-558. PMID: 9806964, PMCID: PMC2229443, DOI: 10.1085/jgp.112.5.549.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBumetanideCarrier ProteinsCells, CulturedChloridesDiureticsHumansKidneyKineticsMutagenesis, Site-DirectedOligonucleotide ProbesPotassiumProtein Structure, TertiaryRecombinant Fusion ProteinsRubidium RadioisotopesSharksSodiumSodium-Potassium-Chloride SymportersSpecies SpecificityThe role of transmembrane domain 2 in cation transport by the Na–K–Cl cotransporter
Isenring P, Jacoby S, Forbush B. The role of transmembrane domain 2 in cation transport by the Na–K–Cl cotransporter. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 7179-7184. PMID: 9618559, PMCID: PMC22778, DOI: 10.1073/pnas.95.12.7179.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterBumetanide-sensitive 86Rb influxTransmembrane domain 2Na-Cl cotransporterBumetanide bindingNa-K-ClHEK-293 cellsHuman cotransportersDomain 2Third transmembrane domainCotransporterNa affinityHEK-293Stable transfectionNKCC2BumetanideCation transportTransmembrane domain 3Transmembrane domainDomain 3Alternative splicingIon transportComparison of Na-K-Cl Cotransporters NKCC1, NKCC2, AND THE HEK CELL Na-K-Cl COTRANSPORTER*
Isenring P, Jacoby S, Payne J, Forbush B. Comparison of Na-K-Cl Cotransporters NKCC1, NKCC2, AND THE HEK CELL Na-K-Cl COTRANSPORTER*. Journal Of Biological Chemistry 1998, 273: 11295-11301. PMID: 9556622, DOI: 10.1074/jbc.273.18.11295.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCell LineHumansKineticsMercuryRNA, MessengerSodium-Potassium-Chloride SymportersConceptsNa-K-Cl cotransporterHEK-293 cellsNa-K-Cl cotransporter NKCC1Epithelial cellsBasolateral Cl- exitHEK-293Reverse transcriptase-polymerase chain reactionNa-K-ClRenal epithelial cellsEpithelial Cl- transportResting level of activityMaintenance of cell volumeSecretory epithelial cellsInhibitor bumetanideCotransporter NKCC1NKCC2 activityCl- exitNKCC1Cl- transportNKCC2CotransporterVolume responseNa affinityResting levelBumetanideThe Na-K-Cl Cotransporters
Haas M, Forbush B. The Na-K-Cl Cotransporters. Journal Of Bioenergetics And Biomembranes 1998, 30: 161-172. PMID: 9672238, DOI: 10.1023/a:1020521308985.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-ClNa-K-Cl cotransport activityNa-K-Cl cotransporter isoformsCotransport activitySecretory epitheliaApical Cl- channelsHypokalemic metabolic alkalosisCation-chloride cotransportersNKCC2 geneCl- channelsBartter's syndromeVolume depletionBasolateral membraneCotransporter proteinApical membraneSalt wastingMetabolic alkalosisSecreting epitheliaNonepithelial cellsAscending limbHenle's loopK-ClCotransporterEpithelial cells
1997
Ion and Bumetanide Binding by the Na-K-Cl Cotransporter
Isenring P, Forbush B. Ion and Bumetanide Binding by the Na-K-Cl Cotransporter. Journal Of Biological Chemistry 1997, 272: 24556-24562. PMID: 9305921, DOI: 10.1074/jbc.272.39.24556.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-ClBumetanide-sensitive 86Rb influxCation-chloride cotransporter familyApparent affinityHEK-293 cellsInhibitor bumetanideCell surface deliveryElectrolyte secretionTime course of activationBumetanidePolarized epitheliaBumetanide bindingCotransporterCl- mediumCotransported ionsHEK-293SNKCC1Hydrophobic central domainSurface deliveryCourse of activationCentral domainTime courseCytoplasmic N-Chimera approach
1996
Na:K:2Cl Cotransporter (NKCC) of Intestinal Epithelial Cells SURFACE EXPRESSION IN RESPONSE TO cAMP*
D'Andrea L, Lytle C, Matthews J, Hofman P, Forbush B, Madara J. Na:K:2Cl Cotransporter (NKCC) of Intestinal Epithelial Cells SURFACE EXPRESSION IN RESPONSE TO cAMP*. Journal Of Biological Chemistry 1996, 271: 28969-28976. PMID: 8910547, DOI: 10.1074/jbc.271.46.28969.Peer-Reviewed Original ResearchConceptsChloride secretionSurface expressionBumetanide-sensitive NaMonoclonal antibodiesIntestinal chloride secretionIncreased surface expressionCell surface expressionEpithelial cell lineNKCC activityT84 monolayersCotransport activityAgonist stimulationCAMP agonistsEpithelial uptakeCotransporterBasolateral domainIntestinal epitheliaSurface biotinylationNKCCConfocal localizationApproximately 6-foldCell linesF-actin cytoskeletonSecretionImmunoelectron microscopyMolecular Cloning and Functional Expression of the K-Cl Cotransporter from Rabbit, Rat, and Human A NEW MEMBER OF THE CATION-CHLORIDE COTRANSPORTER FAMILY*
Gillen C, Brill S, Payne J, Forbush B. Molecular Cloning and Functional Expression of the K-Cl Cotransporter from Rabbit, Rat, and Human A NEW MEMBER OF THE CATION-CHLORIDE COTRANSPORTER FAMILY*. Journal Of Biological Chemistry 1996, 271: 16237-16244. PMID: 8663127, DOI: 10.1074/jbc.271.27.16237.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBrainCarrier ProteinsCell LineChloridesCloning, MolecularDatabases, FactualDNA PrimersDNA, ComplementaryHumansKidneyKineticsModels, StructuralMolecular Sequence DataMultigene FamilyOpen Reading FramesPhylogenyPolymerase Chain ReactionPotassiumProtein Structure, SecondaryRabbitsRatsRecombinant ProteinsRubidiumSequence Homology, Amino AcidSequence Tagged SitesSymportersTransfectionConceptsNa-K-Cl cotransporterK-Cl cotransportK-ClRat brain cDNA libraryThiazide-sensitive Na-Cl cotransporterRate of 86Rb effluxBrain cDNA libraryBumetanide-sensitive Na-K-Cl cotransporterN-linked glycosylation sitesC-terminal regionSubstantial sequence homologyNa-Cl cotransporterNa-K-ClHEK 293) cellsUptake of 86RbNorthern blot analysisGenome sequenceCDNA libraryHydropathy analysisFunctional expressionSequence homologyReverse transcription-polymerase chain reactionHuman embryonic kidneySequence analysisHomologous cDNA probesImmunocytochemical studies of the Na-K-Cl cotransporter of shark kidney
Biemesderfer D, Payne J, Lytle C, Forbush B. Immunocytochemical studies of the Na-K-Cl cotransporter of shark kidney. American Journal Of Physiology 1996, 270: f927-f936. PMID: 8764311, DOI: 10.1152/ajprenal.1996.270.6.f927.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-ClBasolateral membraneCotransporter proteinBasolateral membranes of proximal tubulesNa-K-Cl cotransport proteinShark kidneyBasolateral plasma membraneDistal tubule segmentsApical plasma membraneShark rectal glandDistal nephronReabsorptive epitheliaNaCl reabsorptionPlasma membraneWestern blot analysisTubule segmentsProximal tubulesDiluting segmentWeak stainingShark Squalus acanthiasPresence of multiple isoformsDogfish shark Squalus acanthiasCotransporterMonoclonal antibodiesRegulatory phosphorylation of the secretory Na-K-Cl cotransporter: modulation by cytoplasmic Cl
Lytle C, Forbush B. Regulatory phosphorylation of the secretory Na-K-Cl cotransporter: modulation by cytoplasmic Cl. American Journal Of Physiology 1996, 270: c437-c448. PMID: 8779905, DOI: 10.1152/ajpcell.1996.270.2.c437.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-ClCotransport activityNa-K-Cl cotransport proteinResponse to cell shrinkageIncreased cotransport activityExtracellular K concentrationBlocking activityRefractory to forskolinPhosphatase inhibitor calyculin AInhibitor calyculin AShark rectal glandCotransporter proteinCytoplasmic Cl-CotransporterCell ClSecretory stimuliCell shrinkageCalyculin APhosphorylationRate of entryRegulatory phosphorylationPhosphorylation stateSecretory tubulesRectal gland
1995
Distribution and diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies
Lytle C, Xu J, Biemesderfer D, Forbush B. Distribution and diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies. American Journal Of Physiology 1995, 269: c1496-c1505. PMID: 8572179, DOI: 10.1152/ajpcell.1995.269.6.c1496.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-Cl cotransport proteinNa-K-ClMonoclonal antibodiesEpithelial salt transportCell volume homeostasisT antibodyAscending limb cellsImmunoreactive proteinBinding site densityChloride reabsorptionChloride secretionBasolateral marginsParotid glandCotransporter proteinApical membraneWestern blot analysisVolume homeostasisAcinar cellsWestern blot analysis of membranesCotransporterImmunocytochemical studiesRabbit kidneyAmount of immunoreactive proteinRabbit parotid glandCloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter
Igarashi P, Heuvel G, Payne J, Forbush B. Cloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter. American Journal Of Physiology 1995, 269: f405-f418. PMID: 7573490, DOI: 10.1152/ajprenal.1995.269.3.f405.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterExpression of NKCC2In situ hybridizationCassette exonsRenal Na-K-Cl cotransporterOuter medullaAscending limbAlternative splicingInner stripe of outer medullaPotential sites of phosphorylationAdenosine 3',5'-cyclic monophosphate-dependent protein kinaseDays post coitusFull-length cDNAAnchored polymerase chain reactionSites of phosphorylationConsensus splice donorLoop of HenleS-shaped bodiesProtein kinase CNorthern blot analysisPattern of expressionGenomic clonesNKCC2Outer stripeProtein sequencesLocalization of the renal Na−K−Cl cotransporter gene (Slc 12a1) on mouse Chromosome 2
Quaggin S, Payne J, Forbush B, Igarashi P. Localization of the renal Na−K−Cl cotransporter gene (Slc 12a1) on mouse Chromosome 2. Mammalian Genome 1995, 6: 557-558. PMID: 8589530, DOI: 10.1007/bf00356178.Peer-Reviewed Original ResearchPrimary Structure, Functional Expression, and Chromosomal Localization of the Bumetanide-sensitive Na-K-Cl Cotransporter in Human Colon *
Payne J, Xu J, Haas M, Lytle C, Ward D, Forbush B. Primary Structure, Functional Expression, and Chromosomal Localization of the Bumetanide-sensitive Na-K-Cl Cotransporter in Human Colon *. Journal Of Biological Chemistry 1995, 270: 17977-17985. PMID: 7629105, DOI: 10.1074/jbc.270.30.17977.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBlotting, NorthernBumetanideCarrier ProteinsCell LineChloridesChromosome MappingChromosomes, Human, Pair 5Cloning, MolecularColonDNA, ComplementaryHumansMolecular Sequence DataPotassiumProtein ConformationSodiumSodium-Potassium-Chloride SymportersTumor Cells, CulturedConceptsNa-K-Cl cotransporterT84 cellsRenal Na-K-Cl cotransporterThiazide-sensitive Na-Cl cotransporterBumetanide-sensitive 86Rb influxBumetanide-sensitive Na-K-Cl cotransporterNa-Cl cotransporterHuman colon carcinoma lineNa-K-ClColon carcinoma linePrimary structureHuman embryonic kidney cellsChloride-free mediumShark rectal glandProtein kinase AStably transfected cellsG + C contentEmbryonic kidney cellsElectroneutral cotransporterUrinary bladderCarcinoma linesAbsorptive epitheliaSNKCC1Screening cDNA librariesBiotin-labeled cDNAMolecular characterization of the epithelial NaKCl cotransporter isoforms
Payne J, Forbush B. Molecular characterization of the epithelial NaKCl cotransporter isoforms. Current Opinion In Cell Biology 1995, 7: 493-503. PMID: 7495568, DOI: 10.1016/0955-0674(95)80005-0.Peer-Reviewed Original Research
1994
The molecular basis of chloride transport in shark rectal gland.
Riordan J, Forbush B, Hanrahan J. The molecular basis of chloride transport in shark rectal gland. Journal Of Experimental Biology 1994, 196: 405-418. PMID: 7529818, DOI: 10.1242/jeb.196.1.405.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological Transport, ActiveCarrier ProteinsChloride ChannelsChloridesCystic Fibrosis Transmembrane Conductance RegulatorEpitheliumHomeostasisHumansMembrane ProteinsModels, BiologicalPotassium ChannelsProtein Structure, SecondarySalt GlandSecond Messenger SystemsSharksSodium-Potassium-Chloride SymportersSodium-Potassium-Exchanging ATPaseConceptsApical Cl- channelsCl- channelsProtein kinase ACl- secretionBasolateral transport proteinsTransepithelial Cl- secretionNa+/K(+)-ATPase pumpIntracellular chloride concentrationStimulation of secretionActive Na+ extrusionBasolateral cotransporterShark rectal glandNa+/K+/2Cl- cotransporterCl- movementK+ channelsK+ exitNa+/K(+)-ATPaseApical componentParacellular flowPrimary stimulationEpithelial cellsExcellent experimental modelCotransporterCFTRRectal gland of elasmobranchs