2018
Isoform-Level Interpretation of High-Throughput Proteomics Data Enabled by Deep Integration with RNA-seq
Carlyle B, Kitchen RR, Zhang J, Wilson R, Lam T, Rozowsky JS, Williams KR, Sestan N, Gerstein M, Nairn AC. Isoform-Level Interpretation of High-Throughput Proteomics Data Enabled by Deep Integration with RNA-seq. Journal Of Proteome Research 2018, 17: 3431-3444. PMID: 30125121, PMCID: PMC6392456, DOI: 10.1021/acs.jproteome.8b00310.Peer-Reviewed Original ResearchConceptsRNA-seqProteomic dataGene expressionLiquid chromatography-tandem mass spectrometry proteomicsTandem mass spectrometry proteomicsHigh-throughput proteomic dataTranscriptomic profiling methodsDistinct amino acid sequencesTranscript-level expressionAmino acid sequenceMass spectrometry proteomicsHEK293 cell culturesTranslatome dataMost genesProfound functional implicationsProtein isoformsAlternate isoformsGene productsAcid sequenceCellular controlBiosynthetic stateGeneration of peptidesCell typesFunctional relevanceFunctional implications
2003
Adenylyl cyclase-dependent form of chemical long-term potentiation triggers translational regulation at the elongation step
Chotiner J, Khorasani H, Nairn A, O’Dell T, Watson J. Adenylyl cyclase-dependent form of chemical long-term potentiation triggers translational regulation at the elongation step. Neuroscience 2003, 116: 743-752. PMID: 12573716, DOI: 10.1016/s0306-4522(02)00797-2.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsHippocampusIn Vitro TechniquesLong-Term PotentiationMaleMiceMice, Inbred C57BLProtein BiosynthesisSynaptic TransmissionConceptsEukaryotic elongation factor 2Elongation factor 2Elongation stepProtein synthesisTotal protein synthesisChemical long-term potentiationMessenger RNALong-term potentiationN-methyl-D-aspartate (NMDA) receptor-dependent formInhibition of translationFactor 2Long-term potentiation inductionTranslational regulationProtein ArcAdenylyl cyclase signalingAdenylyl cyclase activationSynaptic activityCyclase signalingN-methyl-D-aspartate (NMDA) receptor activationPersistent maintenanceReceptor-dependent formHippocampal long-term potentiationPhosphorylationRegulationRNA
2002
N-Methyl-D-aspartate receptor activation inhibits protein synthesis in cortical neurons independently of its ionic permeability properties
Gauchy C, Nairn A, Glowinski J, Prémont J. N-Methyl-D-aspartate receptor activation inhibits protein synthesis in cortical neurons independently of its ionic permeability properties. Neuroscience 2002, 114: 859-867. PMID: 12379242, DOI: 10.1016/s0306-4522(02)00322-6.Peer-Reviewed Original ResearchConceptsCortical neuronsAbsence of externalNMDA treatmentTransient cerebral ischemiaAspartate receptor activationGlutamate-induced increaseThapsigargin-sensitive poolMobilization of intracellularProtein synthesisCerebral ischemiaNMDA receptorsNMDAReceptor activationTransient risePresence of externalNeuronsCGP-37157D-serineFree mediumIntracellularIonic permeability propertiesTreatmentSustained releaseIschemiaBlockade
2001
Changes in the phosphorylation of initiation factor eIF‐2α, elongation factor eEF‐2 and p70 S6 kinase after transient focal cerebral ischaemia in mice
Althausen S, Mengesdorf T, Mies G, Oláh L, Nairn A, Proud C, Paschen W. Changes in the phosphorylation of initiation factor eIF‐2α, elongation factor eEF‐2 and p70 S6 kinase after transient focal cerebral ischaemia in mice. Journal Of Neurochemistry 2001, 78: 779-787. PMID: 11520898, DOI: 10.1046/j.1471-4159.2001.00462.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCerebral CortexCerebrovascular CirculationEnzyme InhibitorsEukaryotic Initiation Factor-2ImmunoblottingImmunohistochemistryIschemic Attack, TransientLaser-Doppler FlowmetryMiceMiddle Cerebral ArteryNeuronsPeptide Elongation Factor 2PhosphorylationProtein BiosynthesisRatsRats, WistarRibosomal Protein S6 KinasesThapsigarginConceptsIschaemia-induced changesTransient focal cerebral ischaemiaMiddle cerebral arteryFocal cerebral ischaemiaCerebral ischaemiaP70 S6 kinaseLeft middle cerebral arteryControl levelsTransient cerebral ischaemiaTransient MCA occlusionNeuronal cell injuryPrimary neuronal cell culturesTransient focal ischaemiaElongation factor eEF-2Endoplasmic reticulum calcium pumpEIF-2alpha phosphorylationER calcium homeostasisNeuronal cell culturesS6 kinaseProtein synthesisWestern blot analysisMCA occlusionMCA territoryMin occlusionCerebral arteryAngiotensin II regulates phosphorylation of translation elongation factor-2 in cardiac myocytes
Everett A, Stoops T, Nairn A, Brautigan D. Angiotensin II regulates phosphorylation of translation elongation factor-2 in cardiac myocytes. AJP Heart And Circulatory Physiology 2001, 281: h161-h167. PMID: 11406481, DOI: 10.1152/ajpheart.2001.281.1.h161.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsCells, CulturedChromonesEnzyme InhibitorsMitogen-Activated Protein KinasesMorpholinesMyocardiumPeptide Elongation Factor 2Phosphoprotein PhosphatasesPhosphorylationProtein BiosynthesisProtein Phosphatase 2RatsRats, Sprague-DawleyReceptor, Angiotensin, Type 1Receptor, Angiotensin, Type 2Receptors, AngiotensinSignal TransductionSirolimusConceptsEukaryotic elongation factor 2Mitogen-activated protein kinaseElongation factor 2Protein phosphatase 2A inhibitor okadaic acidTranslation elongation factor 2Protein synthesisInhibitor okadaic acidFactor 2Rapamycin (mTOR) inhibitor rapamycinProtein translationDephosphorylated statePolypeptide elongationII-dependent increaseProtein kinaseEEF2 kinaseOkadaic acidDependent regulationInhibitor FK506MAPK activationPD 98059Cardiac myocytesDephosphorylationInhibitor rapamycinNeonatal cardiac myocytesRat neonatal cardiac myocytesInhibition of protein synthesis in cortical neurons during exposure to hydrogen peroxide
Alirezaei M, Marin P, Nairn A, Glowinski J, Prémont J. Inhibition of protein synthesis in cortical neurons during exposure to hydrogen peroxide. Journal Of Neurochemistry 2001, 76: 1080-1088. PMID: 11181828, DOI: 10.1046/j.1471-4159.2001.00105.x.Peer-Reviewed Original ResearchMeSH KeywordsAniline CompoundsAnimalsCalciumCells, CulturedCerebral CortexDose-Response Relationship, DrugEukaryotic Initiation Factor-2Fluorescent DyesHydrogen PeroxideIntracellular FluidMiceNeuronsPeptide Chain Elongation, TranslationalPeptide Elongation Factor 2PhosphorylationProtein BiosynthesisProtein Synthesis InhibitorsProteinsThapsigarginXanthenesConceptsCortical neuronsGlutamate-induced increaseTransient cerebral ischemiaDose-dependent mannerEffects of thapsigarginProtein synthesisCerebral ischemiaReperfusion periodCommon intracellularEEF-2BlockadeTreatmentNeuronsInhibitionThapsigarginIntracellularPhosphorylationSustained releaseIschemiaEIF-2alphaSlow increaseProtein translationElongation 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 siteThr56ProteinSynthetasesDephosphorylationRibosomes
2000
NMDA receptor-mediated control of protein synthesis at developing synapses
Scheetz A, Nairn A, Constantine-Paton M. NMDA receptor-mediated control of protein synthesis at developing synapses. Nature Neuroscience 2000, 3: 211-216. PMID: 10700251, DOI: 10.1038/72915.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerateAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesCycloheximideElectrophoresis, Gel, Two-DimensionalGlutamic AcidIsoelectric PointMolecular WeightN-MethylaspartatePeptide Elongation Factor 2PhosphorylationPrecipitin TestsProtein BiosynthesisProteinsRatsReceptors, N-Methyl-D-AspartateRetinal Ganglion CellsSuperior ColliculiSynapsesSynaptosomesTime FactorsConceptsNMDAR activationReceptor activationN-methyl-D-aspartate (NMDA) receptor activationActivity-dependent synaptic changesEukaryotic elongation factor 2Receptor-mediated controlSynaptic protein synthesisEEF2 phosphorylationProtein synthesisSuperior colliculiYoung ratsDependent kinase IISynaptic changesLow dosesTotal protein synthesisII synthesisFactor 2Overall protein synthesisActivationElongation factor 2Kinase IIPhosphorylation
1999
Zinc Inhibits Protein Synthesis in Neurons POTENTIAL ROLE OF PHOSPHORYLATION OF TRANSLATION INITIATION FACTOR-2α*
Alirezaei M, Nairn A, Glowinski J, Prémont J, Marin P. Zinc Inhibits Protein Synthesis in Neurons POTENTIAL ROLE OF PHOSPHORYLATION OF TRANSLATION INITIATION FACTOR-2α*. Journal Of Biological Chemistry 1999, 274: 32433-32438. PMID: 10542287, DOI: 10.1074/jbc.274.45.32433.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium ChannelsCells, CulturedEukaryotic Initiation Factor-2LeucineMethionineMiceNeuronsPhosphorylationPolyribosomesProtein BiosynthesisZincConceptsCultured cortical neuronsEukaryotic elongation factor 2Central nervous systemFactor 2Translation initiation factor 2αProtein synthesisCerebral cortexCortical neuronsNervous systemProfound inhibitionSustained increaseBasal levelsTransient increaseBasal ratePotential roleProgressive decreaseInhibits protein synthesisNeuronsAmount of polyribosomesElongation factor 2EIF-2alpha phosphorylationAlpha subunitInhibitionPhosphorylationEukaryotic initiation factor 2
1997
N-methyl-d-aspartate receptor activation and visual activity induce elongation factor-2 phosphorylation in amphibian tecta: A role for N-methyl-d-aspartate receptors in controlling protein synthesis
Scheetz A, Nairn A, Constantine-Paton M. N-methyl-d-aspartate receptor activation and visual activity induce elongation factor-2 phosphorylation in amphibian tecta: A role for N-methyl-d-aspartate receptors in controlling protein synthesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 14770-14775. PMID: 9405688, PMCID: PMC25112, DOI: 10.1073/pnas.94.26.14770.Peer-Reviewed Original ResearchConceptsEukaryotic translation elongation factor 2EEF2 phosphorylationProtein synthesisTranslation elongation factor 2Elongation factor 2 phosphorylationProtein synthetic machinerySubset of proteinsFactor 2 phosphorylationElongation factor 2Synaptic plasticityNMDAR activationNumerous transcriptsProtein translationReceptor activationNew proteinsTranscriptional alterationsSynthetic machineryPhosphorylationN-methyl-D-aspartate (NMDA) receptor activationDendritic localizationN-methyl-D-aspartate receptorsProtein expressionFactor 2Aspartate receptor activationProteinGlutamate-Dependent Phosphorylation of Elongation Factor-2 and Inhibition of Protein Synthesis in Neurons
Marin P, Nastiuk K, Daniel N, Girault J, Czernik A, Glowinski J, Nairn A, Prémont J. Glutamate-Dependent Phosphorylation of Elongation Factor-2 and Inhibition of Protein Synthesis in Neurons. Journal Of Neuroscience 1997, 17: 3445-3454. PMID: 9133370, PMCID: PMC6573691, DOI: 10.1523/jneurosci.17-10-03445.1997.Peer-Reviewed Original ResearchMeSH Keywords6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsAntibody SpecificityCalciumCell SurvivalCells, CulturedCerebral CortexDizocilpine MaleateExcitatory Amino Acid AntagonistsGlutamic AcidMiceNerve Tissue ProteinsNeuronsNeurotoxinsPeptide Elongation Factor 2Peptide Elongation FactorsPhosphorylationProtein BiosynthesisProtein Synthesis InhibitorsReceptors, AMPAReceptors, N-Methyl-D-AspartateConceptsNeuronal deathEukaryotic elongation factor 2Factor 2Cortical neuronsElongation factor 2Glutamate receptorsProtective effectLong-term effectsProtein synthesisPersistent inhibitionPharmacological analysisPharmacological inhibitionCytosolic Ca2Phosphorylation state-specific antibodiesNeuronsNMDAGlutamateInhibitionProtein translationDeathPhosphorylationClose correlationTransient phosphorylationCa2Excitotoxicity
1995
Calcium-dependent regulation of protein synthesis.
Palfrey H, Nairn A. Calcium-dependent regulation of protein synthesis. Advances In Second Messenger And Phosphoprotein Research 1995, 30: 191-223. PMID: 7695990, DOI: 10.1016/s1040-7952(05)80008-4.Peer-Reviewed Original Research
1994
Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins.
Terada N, Patel H, Takase K, Kohno K, Nairn A, Gelfand E. Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 11477-11481. PMID: 7972087, PMCID: PMC45254, DOI: 10.1073/pnas.91.24.11477.Peer-Reviewed Original ResearchConceptsRibosomal proteinsElongation factorProtein synthesisRibosomal protein mRNAsRibosomal protein synthesisTranslation of mRNAsP70 S6 kinaseRibosomal S6 proteinElongation factor 2Higher eukaryotesNonribosomal proteinsPolysomal associationRate of biosynthesisTranslational regulationMammalian cellsMRNA translationS6 kinaseAddition of rapamycinS6 proteinSubsequent phosphorylationEEF-2Translational levelImmunosuppressant rapamycinQuiescent cellsSelective proteinsRole of elongation factor 2 in regulating peptide-chain elongation in the heart
Vary T, Nairn A, Lynch C. Role of elongation factor 2 in regulating peptide-chain elongation in the heart. American Journal Of Physiology 1994, 266: e628-e634. PMID: 7513958, DOI: 10.1152/ajpendo.1994.266.4.e628.Peer-Reviewed Original ResearchConceptsDiabetic ratsEF-2 contentFactor 2Protein synthesisInsulin therapyIncrease of RNADecreased translational efficiencyElongation factor 2RatsDiabetesCardiac muscleImpaired rateDecreased rateProgressive decreaseHeartInhibitionMolecular mechanismsRNA contentPeptide chain elongationH durationTherapyInsulinDecrease
1992
Increased phosphorylation of elongation factor 2 in Alzheimer's disease
Johnson G, Gotlib J, Haroutunian V, Bierer L, Nairn A, Merril C, Wallace W. Increased phosphorylation of elongation factor 2 in Alzheimer's disease. Brain Research 1992, 15: 319-326. PMID: 1331687, DOI: 10.1016/0169-328x(92)90124-t.Peer-Reviewed Original ResearchConceptsDisease brainAlzheimer's diseaseAlzheimer's disease brainFactor 2AD homogenatesAD tissueElongation factor 2Brain homogenatesSame brainDiseaseVariant isoformsProtein synthesisPhosphorylated formInhibits protein synthesisBrainUnaffected areasHomogenatesAcidic isoformsPhosphorylationGene expressionEF-2
1990
Tumor necrosis factor alpha modifies agonist-dependent responses in human neutrophils by inducing the synthesis and myristoylation of a specific protein kinase C substrate.
Thelen M, Rosen A, Nairn A, Aderem A. Tumor necrosis factor alpha modifies agonist-dependent responses in human neutrophils by inducing the synthesis and myristoylation of a specific protein kinase C substrate. Proceedings Of The National Academy Of Sciences Of The United States Of America 1990, 87: 5603-5607. PMID: 2116001, PMCID: PMC54375, DOI: 10.1073/pnas.87.15.5603.Peer-Reviewed Original ResearchMeSH KeywordsColony-Stimulating FactorsGranulocyte-Macrophage Colony-Stimulating FactorGrowth SubstancesHumansIn Vitro TechniquesInterferon-gammaIntracellular Signaling Peptides and ProteinsKineticsLipopolysaccharidesLysineMembrane ProteinsMyristic AcidMyristic AcidsMyristoylated Alanine-Rich C Kinase SubstrateNeutrophilsPhosphatesPhosphopeptidesPhosphorylationProtein BiosynthesisProtein Kinase CProteinsRecombinant ProteinsTumor Necrosis Factor-alphaConceptsSpecific protein kinase C substrateProtein kinase C substrateProtein kinase CC substrateKinase C.Kinase CAlanine-rich C kinase substratePhosphorylation of MARCKSN-terminal glycineC kinase substrateProtein kinase C.Agonist-dependent responsesIdentical phosphopeptidesKinase substrateTransduction pathwaysMARCKS phosphorylationMARCKSEnhanced phosphorylationHuman neutrophilsMurine fibroblastsEffector moleculesProteinPhosphorylationMyristoylationBovine brain