2011
Rare mutations in the human Na-K-Cl cotransporter (NKCC2) associated with lower blood pressure exhibit impaired processing and transport function
Monette MY, Rinehart J, Lifton RP, Forbush B. Rare mutations in the human Na-K-Cl cotransporter (NKCC2) associated with lower blood pressure exhibit impaired processing and transport function. American Journal Of Physiology. Renal Physiology 2011, 300: f840-f847. PMID: 21209010, PMCID: PMC3074999, DOI: 10.1152/ajprenal.00552.2010.Peer-Reviewed Original ResearchConceptsHEK-293 cellsNa-K-Cl cotransporterTransport functionMajor salt transport pathwayPlasma membrane localizationHEK cellsLow transport activitySequence conservationMembrane localizationProtein functionHeterologous expressionXenopus laevis oocytesImportant residuesMutantsRenal salt reabsorptionMolecular mechanismsIndependent mutationsConstitutive activityTransport activityBlood pressureFunctional consequencesImpaired transport functionSuch mutationsProcessing defectsLaevis oocytes
2002
Spatially Distributed Alternative Splice Variants of the Renal Na-K-Cl Cotransporter Exhibit Dramatically Different Affinities for the Transported Ions*
Giménez I, Isenring P, Forbush B. Spatially Distributed Alternative Splice Variants of the Renal Na-K-Cl Cotransporter Exhibit Dramatically Different Affinities for the Transported Ions*. Journal Of Biological Chemistry 2002, 277: 8767-8770. PMID: 11815599, DOI: 10.1074/jbc.c200021200.Peer-Reviewed Original Research
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 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
Molecular 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 probesRegulatory 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
Localization 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
Molecular cloning and functional expression of the bumetanide-sensitive Na-K-Cl cotransporter.
Xu J, Lytle C, Zhu T, Payne J, Benz E, Forbush B. Molecular cloning and functional expression of the bumetanide-sensitive Na-K-Cl cotransporter. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 2201-2205. PMID: 8134373, PMCID: PMC43338, DOI: 10.1073/pnas.91.6.2201.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterBumetanide-sensitive Na-K-Cl cotransporterNa-K-ClNa-K-Cl cotransport activityNa-K-Cl cotransport proteinThiazide-sensitive Na-Cl cotransporterCoupled movement of NaUncharacterized genesShort stretches of homologyRegulation of ionic balanceStretches of homologyC. elegans cDNAHEK-293 cellsHuman HEK-293 cellsPutative transmembrane domainsBumetanide sensitivityCotransport activityCotransporter proteinMovement of NaUrinary bladderAbsorptive epitheliaNorthern blot analysisPhosphoacceptor residuesCDNA sequenceCoding regionKinetic heterogeneity of phosphoenzyme of Na,K-ATPase modeled by unmixed lipid phases. Competence of the phosphointermediate.
Klodos I, Post R, Forbush B. Kinetic heterogeneity of phosphoenzyme of Na,K-ATPase modeled by unmixed lipid phases. Competence of the phosphointermediate. Journal Of Biological Chemistry 1994, 269: 1734-1743. PMID: 8294422, DOI: 10.1016/s0021-9258(17)42089-8.Peer-Reviewed Original Research
1992
The Na-K-Cl cotransport protein of shark rectal gland. I. Development of monoclonal antibodies, immunoaffinity purification, and partial biochemical characterization.
Lytle C, Xu J, Biemesderfer D, Haas M, Forbush B. The Na-K-Cl cotransport protein of shark rectal gland. I. Development of monoclonal antibodies, immunoaffinity purification, and partial biochemical characterization. Journal Of Biological Chemistry 1992, 267: 25428-25437. PMID: 1460038, DOI: 10.1016/s0021-9258(19)74059-9.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, MonoclonalBenzophenonesBlotting, WesternCarrier ProteinsCell MembraneChloridesCholic AcidsChromatography, AffinityChromatography, High Pressure LiquidChromatography, Ion ExchangeDogfishElectrophoresis, Polyacrylamide GelFluorescent Antibody TechniqueMembrane ProteinsMiceMice, Inbred BALB CMolecular Sequence DataMolecular WeightPeptide FragmentsPotassiumRectumSebaceous GlandsSodiumSodium-Potassium-Chloride SymportersSulfanilamidesConceptsNa-K-Cl cotransport proteinNa-K-ClCotransporter proteinNa-K-Cl cotransporterMonoclonal antibodiesShark rectal glandLoop diureticsBasolateral membraneApical membraneTransport of NaRepresentative antibodiesCotransporterCoupled transport of NaAntibodiesPattern of recognitionTreated with N-glycanaseGland secretory cellsImmunoelectron microscopyCell membranePlasma membraneEpitopesPhysiological evidenceSecretory cellsProteolytic fragments
1988
Rapid release of 45Ca from an occluded state of the Na,K-pump.
Forbush B. Rapid release of 45Ca from an occluded state of the Na,K-pump. Journal Of Biological Chemistry 1988, 263: 7970-7978. PMID: 2836404, DOI: 10.1016/s0021-9258(18)68429-7.Peer-Reviewed Original ResearchConceptsNa,K-pumpNa,K-ATPaseK-pumpK-ATPasePhosphorylation of Na,K-ATPaseRelease of 45CaExposure to K+Release of 86RbApparent affinityCa2+Transport sitesK+ congenerMg2+ + ATPIntracellular faceRelease of K+Simultaneous occlusionExtracellular sitesPrevent phosphorylationCa2Exposure to Mg2Extracellular faceReleaseAbsence of PiN-methylglucamineIntracellular mediumPhotoaffinity labelling of a 150 kDa (Na + K + Cl)-cotransport protein from duck red cells with an analog of bumetanide
Haas M, Forbush B. Photoaffinity labelling of a 150 kDa (Na + K + Cl)-cotransport protein from duck red cells with an analog of bumetanide. Biochimica Et Biophysica Acta 1988, 939: 131-144. PMID: 3349075, DOI: 10.1016/0005-2736(88)90054-5.Peer-Reviewed Original ResearchConceptsDuck red cellsRed cellsSimultaneous presence of Na+Binding to intact cellsIncubation mediumDog kidney membraneConsistent with labelingDuck red blood cellsRed blood cellsBumetanideCotransporterRed cell membraneBlood cellsKidney membranesPresence of Na+DucksCellsCell membranePlasma membraneSDS-polyacrylamide gelsIntact cellsSDS-polyacrylamideProteinNorepinephrine
1987
Na,K,Cl-cotransport system: characterization by bumetanide binding and photolabelling.
Haas M, Forbush B. Na,K,Cl-cotransport system: characterization by bumetanide binding and photolabelling. Kidney International Supplement 1987, 23: s134-43. PMID: 3481640.Peer-Reviewed Original ResearchRapid release of 42K and 86Rb from an occluded state of the Na,K-pump in the presence of ATP or ADP.
Forbush B. Rapid release of 42K and 86Rb from an occluded state of the Na,K-pump in the presence of ATP or ADP. Journal Of Biological Chemistry 1987, 262: 11104-11115. PMID: 2440883, DOI: 10.1016/s0021-9258(18)60932-9.Peer-Reviewed Original ResearchRapid release of 42K or 86Rb from two distinct transport sites on the Na,K-pump in the presence of Pi or vanadate.
Forbush B. Rapid release of 42K or 86Rb from two distinct transport sites on the Na,K-pump in the presence of Pi or vanadate. Journal Of Biological Chemistry 1987, 262: 11116-11127. PMID: 2440884, DOI: 10.1016/s0021-9258(18)60933-0.Peer-Reviewed Original ResearchPhysiology and biophysics of chloride and cation cotransport across cell membranes.
Lauf P, McManus T, Haas M, Forbush B, Duhm J, Flatman P, Saier M, Russell J. Physiology and biophysics of chloride and cation cotransport across cell membranes. The FASEB Journal 1987, 46: 2377-94. PMID: 3552736.Peer-Reviewed Original Research
1986
[3H]bumetanide binding to duck red cells. Correlation with inhibition of (Na + K + 2Cl) co-transport.
Haas M, Forbush B. [3H]bumetanide binding to duck red cells. Correlation with inhibition of (Na + K + 2Cl) co-transport. Journal Of Biological Chemistry 1986, 261: 8434-8441. PMID: 3013852, DOI: 10.1016/s0021-9258(19)83931-5.Peer-Reviewed Original ResearchConceptsDuck red cellsExtracellular sodiumRed cellsCo-transportDog kidney outer medullaBinding of [3H]bumetanideConcentration of extracellular sodiumIncreased extracellular sodiumPresence of norepinephrineCo-transport systemBumetanide inhibitionKidney outer medullaOuter medullaBiphasic effectInhibition of influxCell shrinkageHalf-maximalSaturable bindingBumetanideInhibit bindingCell typesSaturable mannerNorepinephrineInfluxBinding to membranes