2010
Chapter 79 The EF2K/MHCK/TRPM7 Family of Atypical Protein Kinases
Wiseman S, Wei F, Nairn A. Chapter 79 The EF2K/MHCK/TRPM7 Family of Atypical Protein Kinases. 2010, 587-599. DOI: 10.1016/b978-0-12-374145-5.00079-6.Peer-Reviewed Original ResearchEF2KProtein synthesisElongation stepAtypical protein kinaseAtypical kinase familySpecific subcellular compartmentsCellular stress pathwaysLocal protein synthesisNeuronal growth conesActivity-dependent regulationKinase familySubcellular compartmentsCatalytic domainKinase domainProtein kinaseEnzymatic functionSecond messengerN-terminalK activityPhosphorylationStress pathwaysGrowth conesParticular Ca2EF2Regulation
2006
2‐Deoxyglucose and NMDA inhibit protein synthesis in neurons and regulate phosphorylation of elongation factor‐2 by distinct mechanisms
Maus M, Torrens Y, Gauchy C, Bretin S, Nairn A, Glowinski J, Premont J. 2‐Deoxyglucose and NMDA inhibit protein synthesis in neurons and regulate phosphorylation of elongation factor‐2 by distinct mechanisms. Journal Of Neurochemistry 2006, 96: 815-824. PMID: 16405506, DOI: 10.1111/j.1471-4159.2005.03601.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimetabolitesBlotting, WesternCalciumCarbonyl Cyanide m-Chlorophenyl HydrazoneCells, CulturedCerebral CortexDeoxyglucoseDose-Response Relationship, DrugDrug InteractionsEmbryo, MammalianEnzyme InhibitorsExcitatory Amino Acid AgonistsIonophoresLeucineMiceModels, BiologicalNeuronsN-MethylaspartateOligomycinsPeptide Elongation Factor 2PhosphorylationProtein KinasesProtein Synthesis InhibitorsPyruvic AcidSodium AzideTime FactorsTOR Serine-Threonine KinasesTritiumConceptsCortical neuronsExcitatory amino acid releaseImine hydrogen maleateNMDA receptor antagonistAMP kinaseAmino acid releaseNeuronal protein synthesisCytosolic free Ca2Protein synthesisCerebral ischaemiaReceptor antagonistBrain damageNeuronal metabolismMetabolic impairmentNMDADistinct mechanismsCytosolic Ca2NeuronsMetabolic deprivationAcid releaseSecondary releaseProtein synthesis inhibitionSynthesis inhibitionElongation factor eEF-2ATP levels
2005
A molecular switch for translational control in taste memory consolidation
Belelovsky K, Elkobi A, Kaphzan H, Nairn A, Rosenblum K. A molecular switch for translational control in taste memory consolidation. European Journal Of Neuroscience 2005, 22: 2560-2568. PMID: 16307598, DOI: 10.1111/j.1460-9568.2005.04428.x.Peer-Reviewed Original ResearchConceptsEukaryotic elongation factor 2Protein synthesisEEF2 phosphorylationKinase 2 activationElongation factor 2Translational regulationTranslation initiationTranslational controlS6K1 phosphorylationMolecular switchSwitch-like effectNeuronal proteinsPhosphorylationElongation rateRate-limiting stepFactor 2Taste memory consolidationSynaptoneurosomal fractionsExpressionTemporal patternsInitiation rateProtein
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 ResearchConceptsEukaryotic 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
Mechanisms for Increased Levels of Phosphorylation of Elongation Factor-2 during Hibernation in Ground Squirrels †
Chen Y, Matsushita M, Nairn A, Damuni Z, Cai D, Frerichs K, Hallenbeck J. Mechanisms for Increased Levels of Phosphorylation of Elongation Factor-2 during Hibernation in Ground Squirrels †. Biochemistry 2001, 40: 11565-11570. PMID: 11560506, DOI: 10.1021/bi010649w.Peer-Reviewed Original ResearchConceptsEukaryotic elongation factor 2EEF-2 phosphorylationElongation factor 2Elongation phaseEEF-2 kinase activityProtein phosphatase 2AGround squirrelsLevel of phosphorylationFactor 2Phosphatase 2ACellular functionsCatalytic subunitUncharacterized mechanismKinase activityInhibitor 2Protein synthesisPhosphorylationPP2AHibernating animalsActive animalsHibernatorsReversible mechanismSevere reductionSquirrelsHibernationChanges 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 ResearchConceptsCultured 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 2Mutation 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
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
1996
Inhibition of Tumor Necrosis Factor Signal Transduction in Endothelial Cells by Dimethylaminopurine*
Marino M, Dunbar J, Wu L, Ngaiza J, Han H, Guo D, Matsushita M, Nairn A, Zhang Y, Kolesnick R, Jaffe E, Donner D. Inhibition of Tumor Necrosis Factor Signal Transduction in Endothelial Cells by Dimethylaminopurine*. Journal Of Biological Chemistry 1996, 271: 28624-28629. PMID: 8910494, DOI: 10.1074/jbc.271.45.28624.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAnimalsCattleEndothelium, VascularEnzyme InhibitorsEukaryotic Initiation Factor-4EHistaminePeptide Elongation Factor 2Peptide Elongation FactorsPeptide Initiation FactorsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene Proteins c-rafSignal TransductionTumor Necrosis Factor-alphaConceptsBovine aortic endothelial cellsElongation factor 2Distinct signal transduction cascadesEukaryotic initiation factor 4ETNF signal transduction pathwayEF-2 phosphorylationC-Jun N-terminal kinaseSignal transduction cascadeInitiation factor 4EProtein kinase activitySignal transduction pathwaysEndothelial cellsN-terminal kinaseTNF actionPhosphorylation cascadeEIF-4ESignal transductionTransduction cascadeTransduction pathwaysResponse of BAECsJun-B expressionKinase activityProtein synthesisPhosphorylationCell types
1995
Rapamycin inhibits ribosomal protein synthesis and induces G1 prolongation in mitogen-activated T lymphocytes.
Terada N, Takase K, Papst P, Nairn A, Gelfand E. Rapamycin inhibits ribosomal protein synthesis and induces G1 prolongation in mitogen-activated T lymphocytes. The Journal Of Immunology 1995, 155: 3418-26. PMID: 7561036, DOI: 10.4049/jimmunol.155.7.3418.Peer-Reviewed Original ResearchConceptsCell cycle progressionRibosomal protein mRNAsCycle progressionG2/M phaseRibosomal proteinsProtein synthesisProtein mRNAG1 prolongationCell cycleS phaseRibosomal protein mRNA translationRibosomal protein synthesisM phaseTotal cellular proteinEffect of rapamycinDNA synthesisNumber of ribosomesCell sizeCellular proteinsMRNA translationEF2K Elongation factor-2 kinase (vertebrates) (CaM-dependent PK III)
Nairn A. EF2K Elongation factor-2 kinase (vertebrates) (CaM-dependent PK III). 1995, 135-136. DOI: 10.1016/b978-012324719-3/50031-5.Peer-Reviewed Original ResearchElongation factor 2EF-2 kinaseElongation factor 2 kinaseYeast EF-2Factor 2EF2KMammalian enzymeSDS-PAGE systemDependent regulationRabbit reticulocytesSubunit sizeExact functionReticulocyte enzymeDifferent isoformsPolypeptide chainProtein synthesisKinaseCell proliferationSame affinityGrowth factorEnzymeDependent inhibitionPhosphorylatesIntracellular calciumCa2
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