2001
Crystal Structure of the Atypical Protein Kinase Domain of a TRP Channel with Phosphotransferase Activity
Yamaguchi H, Matsushita M, Nairn A, Kuriyan J. Crystal Structure of the Atypical Protein Kinase Domain of a TRP Channel with Phosphotransferase Activity. Molecular Cell 2001, 7: 1047-1057. PMID: 11389851, DOI: 10.1016/s1097-2765(01)00256-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsBinding SitesCalcium ChannelsCrystallography, X-RayCyclic AMP-Dependent Protein KinasesEvolution, MolecularMiceModels, MolecularMolecular Sequence DataNucleotidesPhosphotransferasesProtein Structure, SecondaryProtein Structure, TertiarySequence AlignmentTRPC Cation ChannelsZincConceptsEukaryotic protein kinasesProtein kinaseTransient receptor potential channelsCatalytic domainKinase domainProtein kinase domainKinase catalytic domainDetectable sequence similarityATP-grasp domainEukaryotic cellsThreonine residuesSequence similarityChannel kinaseSequence comparisonCatalytic corePotential channelsMetabolic enzymesPhosphotransferase activityKinaseChannel functionTRP channelsExternal signalsUnexpected similaritiesWide distributionProteinTARPP, a novel protein that accompanies TCR gene rearrangement and thymocyte education
Kisielow J, Nairn A, Karjalainen K. TARPP, a novel protein that accompanies TCR gene rearrangement and thymocyte education. European Journal Of Immunology 2001, 31: 1141-1149. PMID: 11298339, DOI: 10.1002/1521-4141(200104)31:4<1141::aid-immu1141>3.0.co;2-r.Peer-Reviewed Original ResearchAgingAmino Acid SequenceAnimalsAntibodiesBase SequenceCD3 ComplexCell DifferentiationCell LineageCells, CulturedCloning, MolecularDown-RegulationFlow CytometryGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Rearrangement, T-LymphocyteMiceMice, Inbred C57BLMolecular Sequence DataMolecular WeightPhosphoproteinsProtein Phosphatase 1Receptors, Antigen, T-CellRNA, MessengerSignal TransductionThymus GlandProtein 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.MutationsRegulationElongation Factor-2 Phosphorylation and the Regulation of Protein Synthesis by Calcium
Nairn A, Matsushita M, Nastiuk K, Horiuchi A, Mitsui K, Shimizu Y, Palfrey H. Elongation Factor-2 Phosphorylation and the Regulation of Protein Synthesis by Calcium. Progress In Molecular And Subcellular Biology 2001, 27: 91-129. PMID: 11575162, DOI: 10.1007/978-3-662-09889-9_4.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCalciumCalcium-Calmodulin-Dependent Protein KinasesCell CycleCell DivisionCyclic AMP-Dependent Protein KinasesCysteine EndopeptidasesElongation Factor 2 KinaseHumansMolecular Sequence DataMultienzyme ComplexesNeuronsPeptide Chain Elongation, TranslationalPeptide Elongation Factor 2PhosphorylationProteasome Endopeptidase ComplexProtein BiosynthesisSequence Homology, Amino AcidSignal TransductionUbiquitinConceptsProtein synthesisElongation factor 2 phosphorylationDephosphorylation of eEF2Eukaryotic protein synthesisAminoacyl-tRNA synthetasesFactor 2 phosphorylationElongation factor 2Ribosomal proteinsRegulated processInitiation factorsDependent kinasesKey proteinsRate of elongationPeptidyl-tRNAPhysiological roleKinasePhosphorylationFactor 2EEF2P siteThr56ProteinSynthetasesDephosphorylationRibosomesDecreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer’s disease
Kim S, Nairn A, Cairns N, Lubec G. Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer’s disease. Journal Of Neural Transmission. Supplementa 2001, 263-272. PMID: 11771749, DOI: 10.1007/978-3-7091-6262-0_21.Peer-Reviewed Original ResearchConceptsARPP-19Protein kinaseDifferential display polymerase chain reactionAlzheimer's diseaseDown syndromeCAMP-dependent protein kinaseTemporal cortexActivity of PKASignal transductionDownregulated sequenceBrain regionsNeurodegenerative disordersDiseaseImpaired mechanismsProtein levelsDecreased activityChain reactionFirst evidenceSignificant reductionSyndromeCortexDisordersTransductionHomologyKinase
2000
The Dopamine/D1 Receptor Mediates the Phosphorylation and Inactivation of the Protein Tyrosine Phosphatase STEP via a PKA-Dependent Pathway
Paul S, Snyder G, Yokakura H, Picciotto M, Nairn A, Lombroso P. The Dopamine/D1 Receptor Mediates the Phosphorylation and Inactivation of the Protein Tyrosine Phosphatase STEP via a PKA-Dependent Pathway. Journal Of Neuroscience 2000, 20: 5630-5638. PMID: 10908600, PMCID: PMC6772528, DOI: 10.1523/jneurosci.20-15-05630.2000.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCatalytic DomainCorpus StriatumCyclic AMP-Dependent Protein KinasesEnzyme ActivationIn Vitro TechniquesMaleMolecular Sequence DataNeuronsPhosphoproteinsPhosphorus RadioisotopesPhosphorylationProtein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyReceptors, Dopamine D1Signal TransductionConceptsProtein tyrosine phosphatase familyCAMP-dependent protein kinaseTryptic phosphopeptide mappingPotential phosphorylation sitesUnique N-terminalProtein-protein interactionsMembrane-associated proteinsRole of phosphorylationTyrosine phosphatase familyAmino acid sequenceSite-directed mutagenesisAmino acid sequencingPKA-dependent pathwayTyrosine phosphatase STEPPhosphatase familyPhosphopeptide mappingPhosphorylation sitesAlternative splicingSubcellular compartmentsProtein kinaseTerminal domainEquivalent residuesCytosolic proteinsSpecific residuesAcid sequenceSevered Molecules Functionally Define the Boundaries of the Cystic Fibrosis Transmembrane Conductance Regulator's Nh2-Terminal Nucleotide Binding Domain
Chan K, Csanády L, Seto-Young D, Nairn A, Gadsby D. Severed Molecules Functionally Define the Boundaries of the Cystic Fibrosis Transmembrane Conductance Regulator's Nh2-Terminal Nucleotide Binding Domain. The Journal Of General Physiology 2000, 116: 163-180. PMID: 10919864, PMCID: PMC2229491, DOI: 10.1085/jgp.116.2.163.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine MonophosphateAnimalsCystic Fibrosis Transmembrane Conductance RegulatorEndoplasmic ReticulumEpitopesFemaleGene DeletionGene ExpressionIon Channel GatingKineticsMembrane PotentialsMolecular Sequence DataMutagenesisOligopeptidesOocytesPatch-Clamp TechniquesPeptide FragmentsPeptidesPrecipitin TestsProtein BindingProtein Structure, TertiarySequence Homology, Amino AcidTransfectionXenopus laevisConceptsR domainCFTR channelsCOOH terminusMature formFull-length CFTRCystic fibrosis transmembrane conductance regulatorAmino acids 590Nucleotide Binding DomainFibrosis transmembrane conductance regulatorExcised patch recordingsChannel activityFamily of ATPRequirement of phosphorylationCFTR channel activityTransmembrane conductance regulatorNBD1 domainSmaller single-channel conductanceCFTR polypeptideTransmembrane domainATP bindingRegulatory domainCassette proteinNBD structuresNBD1Binding domainsCellular Mechanisms Regulating Protein Phosphatase-1 A KEY FUNCTIONAL INTERACTION BETWEEN INHIBITOR-2 AND THE TYPE 1 PROTEIN PHOSPHATASE CATALYTIC SUBUNIT*
Frederick D, Huang H, Yang J, Helps N, Cohen P, Nairn A, DePaoli-Roach A, Tatchell K, Connor J, Shenolikar S. Cellular Mechanisms Regulating Protein Phosphatase-1 A KEY FUNCTIONAL INTERACTION BETWEEN INHIBITOR-2 AND THE TYPE 1 PROTEIN PHOSPHATASE CATALYTIC SUBUNIT*. Journal Of Biological Chemistry 2000, 275: 18670-18675. PMID: 10748125, DOI: 10.1074/jbc.m909312199.Peer-Reviewed Original ResearchConceptsPP1 catalytic subunitCatalytic subunitType 1 protein phosphatase catalytic subunitAmino acidsProtein phosphatase catalytic subunitN-terminusProtein serine/threonineN-terminal 35 amino acidsInhibitor 2Phosphatase catalytic subunitTwo-hybrid analysisNovel regulatory interactionsProtein phosphatase 1Serine/threoninePull-down assaysSite-directed mutagenesisN-terminal sequencePP1 mutantsKey functional interactionsPP1 inhibitorPP1 enzymesPP1 inhibitionPhosphatase 1Regulatory interactionsSaccharomyces cerevisiaeRegulation of protein phosphatase-1
Aggen J, Nairn A, Chamberlin R. Regulation of protein phosphatase-1. Cell Chemical Biology 2000, 7: r13-r23. PMID: 10662690, DOI: 10.1016/s1074-5521(00)00069-7.Peer-Reviewed Original Research
1999
Regulation of Neurabin I Interaction with Protein Phosphatase 1 by Phosphorylation †
McAvoy T, Allen P, Obaishi H, Nakanishi H, Takai Y, Greengard P, Nairn A, Hemmings H. Regulation of Neurabin I Interaction with Protein Phosphatase 1 by Phosphorylation †. Biochemistry 1999, 38: 12943-12949. PMID: 10504266, DOI: 10.1021/bi991227d.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1Neurabin IPP1 activityPhosphatase 1Two-hybrid interaction analysisActin-binding proteinsCo-immunoprecipitation experimentsMimic phosphorylationSerine 461Phosphorylated residuesGlutathione S-transferaseOverlay assaysFusion proteinSignaling mechanismGamma isoformsCAMP pathwayPhosphorylationS-transferaseProteinTryptic digestPKARegulationHPLC-MS analysisInteraction analysisS461Modulation of GT-1 DNA-binding activity by calcium-dependent phosphorylation
Maréchal E, Hiratsuka K, Delgado J, Nairn A, Qin J, Chait B, Chua N. Modulation of GT-1 DNA-binding activity by calcium-dependent phosphorylation. Plant Molecular Biology 1999, 40: 373-386. PMID: 10437822, DOI: 10.1023/a:1006131330930.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsArabidopsisBase SequenceBinding SitesCalciumCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesDNA PrimersDNA-Binding ProteinsIn Vitro TechniquesMolecular Sequence DataNuclear ProteinsPhosphorylationPlants, ToxicRatsRecombinant ProteinsSequence Homology, Amino AcidSubstrate SpecificityTranscription FactorsConceptsDNA-binding activityCalcium-dependent phosphorylationGene expressionMolecular switchGT-1Analysis of mutantsDNA-binding proteinsLight-grown plantsPost-translational modificationsCalf intestine phosphataseCalcium/calmodulin kinasePhosphorylatable residuesCasein kinaseGene activationMass spectrometry analysisPromoter sequencesDNA bindingKinase activityBoxIICalmodulin kinasePhosphorylationHGT-1Novo synthesisDephosphorylationSpectrometry analysisPhylogenetically conserved CK‐II phosphorylation site of the murine homeodomain protein Hoxb‐6
Fienberg A, Nordstedt C, Belting H, Czernik A, Nairn A, Gandy S, Greengard P, Ruddle F. Phylogenetically conserved CK‐II phosphorylation site of the murine homeodomain protein Hoxb‐6. Journal Of Experimental Zoology 1999, 285: 76-84. PMID: 10327653, DOI: 10.1002/(sici)1097-010x(19990415)285:1<76::aid-jez9>3.0.co;2-k.Peer-Reviewed Original ResearchConceptsTwo-dimensional tryptic phosphopeptide mappingTryptic phosphopeptide mappingHoxb-6Casein kinase IIHomeodomain proteinsPhosphopeptide mappingPhosphorylation sitesHoxc-8Protein kinaseSf9 cellsCasein kinase II phosphorylation sitesKinase IICK-II phosphorylation sitesCAMP-dependent protein kinaseSignal transduction mechanismsBaculovirus expression systemProtein functionPhosphorylation stateMouse embryonic spinal cordExpression systemSerine 214Embryonic spinal cordTransduction mechanismsKinaseProteinMolecular identification of human G-substrate, a possible downstream component of the cGMP-dependent protein kinase cascade in cerebellar Purkinje cells
Endo S, Suzuki M, Sumi M, Nairn A, Morita R, Yamakawa K, Greengard P, Ito M. Molecular identification of human G-substrate, a possible downstream component of the cGMP-dependent protein kinase cascade in cerebellar Purkinje cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 2467-2472. PMID: 10051666, PMCID: PMC26808, DOI: 10.1073/pnas.96.5.2467.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBrainCerebellumCloning, MolecularCyclic GMP-Dependent Protein KinasesDatabases as TopicExpressed Sequence TagsHumansMolecular Sequence DataNerve Tissue ProteinsPurkinje CellsRabbitsRecombinant ProteinsRNA, MessengerSequence AlignmentSequence Homology, Amino AcidTranscription, GeneticConceptsAmino acid sequenceProtein phosphatase 1G-substrateAcid sequencePhosphatase 1Deduced amino acid sequenceRadiation hybrid panel analysisProtein phosphatase 2APutative phosphorylation sitesCGMP-dependent protein kinaseProtein kinase cascadeProtein phosphatase inhibitorSequence tag databaseSites of phosphorylationVitro translation productsHuman brain libraryCGMP-dependent proteinAcid-soluble proteinsApparent molecular massSDS/PAGEPhosphatase 2AThr-35Kinase cascadePhosphorylation sitesTag databaseCharacterization of the Inhibition of Protein Phosphatase-1 by DARPP-32 and Inhibitor-2*
Huang H, Horiuchi A, Watanabe T, Shih S, Tsay H, Li H, Greengard P, Nairn A. Characterization of the Inhibition of Protein Phosphatase-1 by DARPP-32 and Inhibitor-2*. Journal Of Biological Chemistry 1999, 274: 7870-7878. PMID: 10075680, DOI: 10.1074/jbc.274.12.7870.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsCatalytic DomainDopamine and cAMP-Regulated Phosphoprotein 32Enzyme InhibitorsHumansMolecular Sequence DataMolecular WeightMuscle ProteinsMutagenesis, Site-DirectedNerve Tissue ProteinsPhosphoprotein PhosphatasesPhosphoproteinsPhosphorylationProtein Phosphatase 1ProteinsRabbitsSerineThreonine
1998
Characterization of the Mechanism of Regulation of Ca2+/ Calmodulin-dependent Protein Kinase I by Calmodulin and by Ca2+/Calmodulin-dependent Protein Kinase Kinase*
Matsushita M, Nairn A. Characterization of the Mechanism of Regulation of Ca2+/ Calmodulin-dependent Protein Kinase I by Calmodulin and by Ca2+/Calmodulin-dependent Protein Kinase Kinase*. Journal Of Biological Chemistry 1998, 273: 21473-21481. PMID: 9705275, DOI: 10.1074/jbc.273.34.21473.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCalcium-Calmodulin-Dependent Protein Kinase KinaseCalcium-Calmodulin-Dependent Protein Kinase Type 1Calcium-Calmodulin-Dependent Protein Kinase Type 4Calcium-Calmodulin-Dependent Protein KinasesCalmodulinCloning, MolecularEnzyme ActivationKineticsMolecular Sequence DataPhosphorylationProtein Serine-Threonine KinasesRatsConceptsProtein kinase IAbsence of CaMKinase ICalmodulin-dependent protein kinase IDetailed structure-function analysisDependent protein kinase IDependent protein kinase kinaseProtein kinase kinaseStructure-function analysisMechanism of regulationSpecific amino acidsEnzyme activityKinase kinaseAutoinhibited stateRegulatory domainCatalytic coreCaMKIMutant formsBasal enzyme activitySecond enzymeCaMKKAmino acidsAdditional mutationsMutationsActive formIsolation 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 modelsInhibitorsSubunitsProteinPathwayCharacterization of the interaction between DARPP-32 and protein phosphatase 1 (PP-1): DARPP-32 peptides antagonize the interaction of PP-1 with binding proteins
Kwon Y, Huang H, Desdouits F, Girault J, Greengard P, Nairn A. Characterization of the interaction between DARPP-32 and protein phosphatase 1 (PP-1): DARPP-32 peptides antagonize the interaction of PP-1 with binding proteins. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 3536-3541. PMID: 9108011, PMCID: PMC20474, DOI: 10.1073/pnas.94.8.3536.Peer-Reviewed Original ResearchConceptsPP-1cPP-1C.PP-1DARPP-32Inhibitor 2Protein phosphatase 1Amino acid sequence analysisAmino acid residuesNH2-terminal regionAcid sequence analysisPhosphoinhibitor-1Threonine residuesPhosphatase 1Inhibitor-1Catalytic subunitCalyculin AOkadaic acidInhibitor proteinActive siteAcid residuesSequence analysisProteinEnzyme activityMotifResiduesThe Cytoplasmic Domain of Alzheimer’s Amyloid Precursor Protein Is Phosphorylated at Thr654, Ser655, and Thr668 in Adult Rat Brain and Cultured Cells
Oishi M, Nairn A, Czernik A, Lim G, Isohara T, Gandy S, Greengard P, Suzuki T. The Cytoplasmic Domain of Alzheimer’s Amyloid Precursor Protein Is Phosphorylated at Thr654, Ser655, and Thr668 in Adult Rat Brain and Cultured Cells. Molecular Medicine 1997, 3: 111-123. PMID: 9085254, PMCID: PMC2230054, DOI: 10.1007/bf03401803.Peer-Reviewed Original ResearchConceptsAlzheimer's disease amyloid precursor proteinCytoplasmic domainCultured cell linesCell cycle-dependent mannerAmyloid precursor proteinCultured cellsCycle-dependent mannerPhosphorylation state-specific antibodiesPhosphorylation-specific antibodiesPrecursor proteinCell linesProtein kinase C.Stoichiometric phosphorylationG2/M phaseAPP isoformsThr654Alzheimer amyloid precursor proteinOkadaic acidBiological functionsCell cycleKinase C.Intact cellsPhosphorylationHeLa cellsSpecific inhibitor
1996
Structural Basis for the Autoinhibition of Calcium/Calmodulin-Dependent Protein Kinase I
Goldberg J, Nairn A, Kuriyan J. Structural Basis for the Autoinhibition of Calcium/Calmodulin-Dependent Protein Kinase I. Cell 1996, 84: 875-887. PMID: 8601311, DOI: 10.1016/s0092-8674(00)81066-1.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBinding SitesCalcium-Calmodulin-Dependent Protein Kinase Type 1Calcium-Calmodulin-Dependent Protein KinasesCrystallographyImage Processing, Computer-AssistedMolecular Sequence DataPhosphorylationProtein ConformationProtein KinasesRatsSequence Homology, Amino AcidSubstrate SpecificityConceptsCalmodulin-dependent protein kinase ICalcium/calmodulin-dependent protein kinase IProtein kinase IKinase IRegulatory regionsATP-binding domainTerminal regulatory regionCatalytic domainCatalytic coreSecond helixStructural basisAlpha-helixCalmodulin targetsConformational changesPeptide substratesHelix segmentsCalmodulinHelixSubstantial structural changesRecognition elementInitial interactionInhibitory interactionsDomainAutoinhibitionCrystal structure