2022
Myosin light chain phosphatase catalytic subunit dephosphorylates cardiac myosin via mechanisms dependent and independent of the MYPT regulatory subunits
Lee E, Liu Z, Nguyen N, Nairn A, Chang AN. Myosin light chain phosphatase catalytic subunit dephosphorylates cardiac myosin via mechanisms dependent and independent of the MYPT regulatory subunits. Journal Of Biological Chemistry 2022, 298: 102296. PMID: 35872014, PMCID: PMC9418503, DOI: 10.1016/j.jbc.2022.102296.Peer-Reviewed Original ResearchConceptsMyosin light chain phosphataseRegulatory light chainRegulatory subunitCatalytic subunitPhosphatase catalytic subunitMain catalytic subunitSmooth muscle myosin light chain phosphataseNon-muscle cellsMuscle myosin light chain phosphataseMyosin regulatory light chainMyosin light chain kinaseLight chain kinasePP1cβTrimeric proteinConditional knockout miceLight chain phosphatasePhosphatase activitySubunitsPhosphate/Chain kinaseMuscle pathogenesisPhysiological regulationKnockout animalsMain isoformsProtein
2018
Striatin-1 is a B subunit of protein phosphatase PP2A that regulates dendritic arborization and spine development in striatal neurons
Li D, Musante V, Zhou W, Picciotto MR, Nairn AC. Striatin-1 is a B subunit of protein phosphatase PP2A that regulates dendritic arborization and spine development in striatal neurons. Journal Of Biological Chemistry 2018, 293: 11179-11194. PMID: 29802198, PMCID: PMC6052221, DOI: 10.1074/jbc.ra117.001519.Peer-Reviewed Original ResearchConceptsSerine/threonine phosphatase PP2AStriatin-interacting phosphataseRNA knockdown approachB subunitSTRIPAK complexPhosphatase PP2AProtein phosphataseMultiprotein complexesKnockdown approachStriatin familyMutant constructsStriatal neuronal culturesPP2ANeuronal developmentPrimary striatal neuronal culturesDendritic phenotypeKnockdown modelSynapse formationSubunitsSpine developmentSelective roleReduced expressionNeuron maturationNeuronal culturesStriatal neurons
2001
Protein phosphatase 1 regulation by inhibitors and targeting subunits
Watanabe T, Huang H, Horiuchi A, da Cruze Silva E, Hsieh-Wilson L, Allen P, Shenolikar S, Greengard P, Nairn A. Protein phosphatase 1 regulation by inhibitors and targeting subunits. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 3080-3085. PMID: 11248035, PMCID: PMC30610, DOI: 10.1073/pnas.051003898.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell LineChromosomal Proteins, Non-HistoneDNA-Binding ProteinsDopamine and cAMP-Regulated Phosphoprotein 32Enzyme InhibitorsGene ExpressionHistone ChaperonesMicrofilament ProteinsMolecular Sequence DataMyelin Basic ProteinNerve Tissue ProteinsPhosphoprotein PhosphatasesPhosphoproteinsProtein Phosphatase 1ProteinsRabbitsRecombinant Fusion ProteinsSpodopteraSubstrate SpecificityTranscription FactorsConceptsProtein phosphatase 1Native protein phosphatase-1PP1 nuclear targeting subunitPhosphotyrosine-containing substratesInhibitor 2Protein phosphatase 1 regulationRecombinant protein phosphatase 1Sf9 insect cellsC-terminal sequencesLoss of interactionTargeting subunitPP1/Phosphatase 1Insect cellsResidues 274Inhibitor proteinRecombinant proteinsProtein inhibitorSubunitsEscherichia coliY272Corresponding regionPhosphorylase a.MutationsRegulation
1999
Mutation of Tyr307 and Leu309 in the Protein Phosphatase 2A Catalytic Subunit Favors Association with the α4 Subunit Which Promotes Dephosphorylation of Elongation Factor-2 †
Chung H, Nairn A, Murata K, Brautigan D. Mutation of Tyr307 and Leu309 in the Protein Phosphatase 2A Catalytic Subunit Favors Association with the α4 Subunit Which Promotes Dephosphorylation of Elongation Factor-2 †. Biochemistry 1999, 38: 10371-10376. PMID: 10441131, DOI: 10.1021/bi990902g.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnion Exchange ResinsBacterial ProteinsCatalytic DomainChromatography, Ion ExchangeCOS CellsHemagglutininsLectinsLeucineMutagenesis, Site-DirectedOligopeptidesPeptide Elongation Factor 2Peptide Elongation FactorsPeptidesPhosphoprotein PhosphatasesPhosphoproteinsPhosphorylationPrecipitin TestsProtein Phosphatase 2Resins, SyntheticTransfectionTyrosineConceptsAlpha 4 proteinElongation factor 2AC dimerC subunitSpecific intracellular substratesProtein phosphatase 2ASites of phosphorylationAbc trimerCOS-7 cellsFactor 2B subunitC-terminal residuesTOR proteinsPhosphatase 2ANovel subunitCatalytic subunitTransient overexpressionSubstrate specificityCellular locationIntracellular substratesTransient expressionP70S6 kinaseSingle mutationProtein synthesisSubunits
1998
Isolation and Characterization of PNUTS, a Putative Protein Phosphatase 1 Nuclear Targeting Subunit*
Allen P, Kwon Y, Nairn A, Greengard P. Isolation and Characterization of PNUTS, a Putative Protein Phosphatase 1 Nuclear Targeting Subunit*. Journal Of Biological Chemistry 1998, 273: 4089-4095. PMID: 9461602, DOI: 10.1074/jbc.273.7.4089.Peer-Reviewed Original ResearchConceptsPhosphatase 1 nuclear targeting subunitProtein phosphatase 1Targeting subunitPP1 catalytic activityMammalian cell lysatesTwo-hybrid assayPP1 functionsNuclear functionsNuclear compartmentalizationNovel proteinPhosphatase 1Subcellular localizationCell physiologyCell lysatesCell nucleiSubunitsExogenous substratesInitial characterizationProteinStable complexesPotent modulationChromatinCloningMitosisCompartmentalization
1997
A molecular modeling analysis of the binding interactions between the okadaic acid class of natural product inhibitors and the ser-thr phosphatases, PP1 and PP2A
Gauss C, Sheppeck J, Nairn A, Chamberlin R. A molecular modeling analysis of the binding interactions between the okadaic acid class of natural product inhibitors and the ser-thr phosphatases, PP1 and PP2A. Bioorganic & Medicinal Chemistry 1997, 5: 1751-1773. PMID: 9354231, DOI: 10.1016/s0968-0896(97)00145-4.Peer-Reviewed Original ResearchConceptsSerine-threonine proteinOkadaic acid classSignal transduction pathwaysNatural product inhibitorsCatalytic subunitTransduction pathwaysPP1Endogenous substratesProduct inhibitorsMolecular modeling analysisSer-ThrAcid classPP2AImportant roleComputer-generated modelsInhibitorsSubunitsProteinPathway
1995
Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1
Goldberg J, Huang H, Kwon Y, Greengard P, Nairn A, Kuriyan J. Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature 1995, 376: 745-753. PMID: 7651533, DOI: 10.1038/376745a0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesCatalysisCrystallography, X-RayDopamine and cAMP-Regulated Phosphoprotein 32Escherichia coliHumansIntracellular Signaling Peptides and ProteinsMetalsMicrocystinsModels, MolecularMolecular Sequence DataNerve Tissue ProteinsNuclear ProteinsPeptides, CyclicPhosphoprotein PhosphatasesPhosphoproteinsProtein ConformationProtein Phosphatase 1ProteinsRabbitsRecombinant ProteinsRNA-Binding ProteinsSequence Homology, Amino AcidConceptsPhosphatase 1Protein serine/threonine phosphatase-1Serine/threonine phosphatase 1Mammalian protein phosphatase 1Protein phosphatase 1Potential binding sitesThree-dimensional structureCatalytic subunitRegulatory sequencesCatalytic domainCarboxy terminusΒ scaffoldBinding sitesActive siteSurface groovesTerminusSubunitsDomainProteinCrystal structureSitesTyrosineMetalloenzymesSequenceToxin
1994
Identification of the phosphorylation site for cAMP-dependent protein kinase on Na+,K(+)-ATPase and effects of site-directed mutagenesis.
Fisone G, Cheng S, Nairn A, Czernik A, Hemmings H, Höög J, Bertorello A, Kaiser R, Bergman T, Jörnvall H. Identification of the phosphorylation site for cAMP-dependent protein kinase on Na+,K(+)-ATPase and effects of site-directed mutagenesis. Journal Of Biological Chemistry 1994, 269: 9368-9373. PMID: 7510709, DOI: 10.1016/s0021-9258(17)37117-x.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-3-isobutylxanthineAmino Acid SequenceAnimalsBase SequenceColforsinCyclic AMP-Dependent Protein KinasesDNA PrimersKineticsMolecular Sequence DataMutagenesis, Site-DirectedPeptide MappingPeptidesPhosphoserineRatsRecombinant ProteinsSodium-Potassium-Exchanging ATPaseStructure-Activity RelationshipConceptsCAMP-dependent protein kinasePhosphorylation sitesProtein kinaseSignal transduction pathwaysWild-type enzymeSite-directed mutagenesisATPase alpha subunitAlpha 1 isoformCatalytic subunitTransduction pathwaysDependent phosphorylationSeryl residuesCOS cellsAlpha subunitIntact cellsATPaseKinasePhosphorylationEnzymeSubunitsCellsExperimental approachMutagenesisCDNAIsoforms
1992
The protein kinase A-regulated cardiac CI− channel resembles the cystic fibrosis transmembrane conductance regulator
Nagel G, Hwang T, Nastiuk K, Nairn A, Gadsbyt D. The protein kinase A-regulated cardiac CI− channel resembles the cystic fibrosis transmembrane conductance regulator. Nature 1992, 360: 81-84. PMID: 1279437, DOI: 10.1038/360081a0.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBiological Transport, ActiveBlotting, NorthernChloride ChannelsChlorineCystic Fibrosis Transmembrane Conductance RegulatorGuanosine TriphosphateGuinea PigsIn Vitro TechniquesIon Channel GatingMembrane PotentialsMembrane ProteinsMyocardiumPhosphorylationProtein KinasesReceptors, Adrenergic, betaRNAConceptsCystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorConductance regulatorCyclic AMP-dependent protein kinaseAMP-dependent protein kinasePKA catalytic subunitResult of phosphorylationPhosphorylated channelsCatalytic subunitProtein kinaseSingle-channel conductanceNucleoside triphosphatesPhosphorylationMembrane potentialEpithelial cellsChannel activationRegulatorChannel conductanceCystic fibrosisKinaseCardiac ventricular myocytesSubunitsProteinUnitary current amplitude
1989
Chloride conductance regulated by cyclic AMP-dependent protein kinase in cardiac myocytes
Bahinski A, Nairn A, Greengard P, Gadsby D. Chloride conductance regulated by cyclic AMP-dependent protein kinase in cardiac myocytes. Nature 1989, 340: 718-721. PMID: 2475783, DOI: 10.1038/340718a0.Peer-Reviewed Original ResearchConceptsCyclic AMP-dependent protein kinaseAMP-dependent protein kinaseProtein kinaseChloride ion currentCatalytic subunitRegulatory proteinsKinase activationIon channelsKinaseChloride conductanceCalcium entrySingle-channel currentsCardiac myocytesCellsHeart cellsPhosphorylationAction potential repolarizationConductanceSubunitsProteinIntracellular dialysisMyocytesRegulationChannel currentsAdrenergic stimulation
1988
Autophosphorylation and activation of Ca2+/calmodulin-dependent protein kinase II in intact nerve terminals.
Gorelick FS, Wang JK, Lai Y, Nairn AC, Greengard P. Autophosphorylation and activation of Ca2+/calmodulin-dependent protein kinase II in intact nerve terminals. Journal Of Biological Chemistry 1988, 263: 17209-17212. PMID: 2846557, DOI: 10.1016/s0021-9258(19)77816-8.Peer-Reviewed Original ResearchConceptsDependent protein kinase IIKinase IIAlpha subunitProtein kinase IIKinase II activityTwo-dimensional phosphopeptide mapsII activityState of phosphorylationAutophosphorylation mechanismThreonine residuesPhosphothreonine contentPhosphopeptide mapsTransient phosphorylationIndependent speciesPhosphoserine contentIntact nerve terminalsBeta subunitEnhanced phosphorylationSubunitsPhosphorylationAutophosphorylationIntact synaptosomesBasal incubation conditionsPhosphopeptidesDepolarization of synaptosomesCa2+/calmodulin-dependent protein kinase II: identification of threonine-286 as the autophosphorylation site in the alpha subunit associated with the generation of Ca2+-independent activity.
Thiel G, Czernik AJ, Gorelick F, Nairn AC, Greengard P. Ca2+/calmodulin-dependent protein kinase II: identification of threonine-286 as the autophosphorylation site in the alpha subunit associated with the generation of Ca2+-independent activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 1988, 85: 6337-6341. PMID: 2842767, PMCID: PMC281965, DOI: 10.1073/pnas.85.17.6337.Peer-Reviewed Original ResearchConceptsBeta/beta' subunitsAlpha subunitThr-286Beta subunitDependent protein kinase IIProtein kinase IIAutophosphorylation sitesThreonine residuesMajor phosphopeptideNaDodSO4/PAGEPhosphorylated residuesCyanogen bromide peptidesConsensus sequenceKinase IIIndependent activityThermolytic phosphopeptidesPrimary structureGas-phase Edman degradationGeneration of Ca2Edman degradationAutophosphorylationSubunitsThreonine-286Amino acidsAsp-Xaa
1984
The amino acid sequence of rabbit skeletal muscle calmodulin
Nairn A, Grand R, Perry S. The amino acid sequence of rabbit skeletal muscle calmodulin. FEBS Letters 1984, 167: 215-220. PMID: 6698209, DOI: 10.1016/0014-5793(84)80129-5.Peer-Reviewed Original ResearchConceptsSingle polypeptide chainMyosin light chain kinaseBlocked N terminusRabbit skeletal muscleLight chain kinasePhosphorylase kinaseMammalian calmodulinN-terminusPolypeptide chainResidues 48Chain kinaseAmide assignmentsCalmodulinLow ionic strength bufferKinaseSkeletal muscleIonic strength bufferSequenceN-terminal tripeptideStrength bufferTerminal tripeptideTerminusSubunitsProteinResidues