2017
Reciprocal regulation of ARPP-16 by PKA and MAST3 kinases provides a cAMP-regulated switch in protein phosphatase 2A inhibition
Musante V, Li L, Kanyo J, Lam TT, Colangelo CM, Cheng SK, Brody AH, Greengard P, Le Novère N, Nairn AC. Reciprocal regulation of ARPP-16 by PKA and MAST3 kinases provides a cAMP-regulated switch in protein phosphatase 2A inhibition. ELife 2017, 6: e24998. PMID: 28613156, PMCID: PMC5515580, DOI: 10.7554/elife.24998.Peer-Reviewed Original ResearchConceptsARPP-16ARPP-19Protein phosphatase 2A inhibitionProtein phosphatase PP2A.Inhibition of PP2ASwitch-like responseKinase inhibitsPhosphatase PP2A.Regulatory interactionsPKA phosphorylationAntagonistic interplayReciprocal regulationBasal phosphorylationPhosphorylationMAST3PP2APKAENSAKinaseStriatal signalingPP2A.Multiple sitesInhibitionMitosisSignaling
2003
Chapter 95 Atypical Protein Kinases The EF2/MHCK/ChaK Kinase Family
Nairn A. Chapter 95 Atypical Protein Kinases The EF2/MHCK/ChaK Kinase Family. 2003, 567-573. DOI: 10.1016/b978-012124546-7/50456-3.Peer-Reviewed Original ResearchProtein kinaseCatalytic domainAtypical protein kinaseProtein kinase AAnalysis of sequencesPhosphorylate serineAtypical kinaseProtein superfamiliesKinase familySignal transductionEvolutionary linkEnzyme classesSubstrate specificityKinase ADistinct membersTyrosine residuesMetabolic enzymesKinaseAmino acidsCatalytic mechanismIndividual functionsDetailed structural analysisEnzymeFamilyStructural features
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 distributionProteinAuto‐inhibition of Ca2+/calmodulin‐dependent protein kinase II by its ATP‐binding domain
Lengyel I, Nairn A, McCluskey A, Tóth G, Penke B, Rostas J. Auto‐inhibition of Ca2+/calmodulin‐dependent protein kinase II by its ATP‐binding domain. Journal Of Neurochemistry 2001, 76: 1066-1072. PMID: 11181826, DOI: 10.1046/j.1471-4159.2001.00139.x.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBinding SitesCalcium-Calmodulin-Dependent Protein Kinase Type 1Calcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein Kinase Type 4Calcium-Calmodulin-Dependent Protein KinasesCyclic AMP-Dependent Protein KinasesDose-Response Relationship, DrugEnzyme ActivationEnzyme InhibitorsPeptide FragmentsPeptidesProtein Structure, TertiaryRatsSubstrate SpecificityConceptsATP-binding domainDependent protein kinase IIProtein kinase IIProtein kinaseCaMPK-IIKinase IICAMP-dependent protein kinaseDependent protein kinaseSubstitution of phenylalaninePhysiological processesKey enzymeAutocamtide-2Position 25Phenylalanine 25Molecular interactionsKinasePeptide fragmentsDependent activityIndependent activityATPEnzymeCrucial roleIntramolecular interactionsDomainInhibitionElongation 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
Novel compounds, ‘1,3-selenazine derivatives’ as specific inhibitors of eukaryotic elongation factor-2 kinase
Cho S, Koketsu M, Ishihara H, Matsushita M, Nairn A, Fukazawa H, Uehara Y. Novel compounds, ‘1,3-selenazine derivatives’ as specific inhibitors of eukaryotic elongation factor-2 kinase. Biochimica Et Biophysica Acta 2000, 1475: 207-215. PMID: 10913818, DOI: 10.1016/s0304-4165(00)00061-1.Peer-Reviewed Original ResearchConceptsV-src-transformed NIH3T3 cellsEukaryotic elongation factor 2 kinaseProtein kinase AElongation factor 2 kinaseProtein kinase CProtein tyrosine kinasesEEF-2KProtein kinaseEEF-2K inhibitorNIH3T3 cellsCalmodulin-dependent protein kinaseV-Src kinaseMultiple protein kinasesCalmodulin-dependent protein kinase IIProtein levelsK inhibitorsProtein kinase IIEEF-2K.Kinase AKinase IITyrosine kinaseKinase CKinaseTs-4Specific inhibitor
1999
Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons
Bibb J, Snyder G, Nishi A, Yan Z, Meijer L, Fienberg A, Tsai L, Kwon Y, Girault J, Czernik A, Huganir R, Hemmings H, Nairn A, Greengard P. Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons. Nature 1999, 402: 669-671. PMID: 10604473, DOI: 10.1038/45251.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCDC2 Protein KinaseCyclic AMP-Dependent Protein KinasesCyclin-Dependent Kinase 5Cyclin-Dependent KinasesDopamineDopamine and cAMP-Regulated Phosphoprotein 32Enzyme InhibitorsIn Vitro TechniquesMiceNerve Tissue ProteinsNeuronsPhosphoproteinsPhosphorylationRecombinant ProteinsSignal TransductionThreonineConceptsProtein kinase APhospho-ThrDARPP-32Serine/threonine phosphataseSerine/threonine kinaseInhibitor of PKAProtein phosphatase 1Signal transduction moleculesParticular amino acid residuesSignal transduction mechanismsAmino acid residuesCyclin-dependent kinase 5Threonine phosphataseThreonine 75PKA substratesThreonine kinasePhosphatase 1Phosphatase inhibitorProtein kinaseTransduction moleculesKinase ASingle proteinKinase 5Transduction mechanismsKinasePhosphorylation of the Cytoplasmic Domain of Alzheimer's β-Amyloid Precursor Protein at Ser655 by a Novel Protein Kinase
Isohara T, Horiuchi A, Watanabe T, Ando K, Czernik A, Uno I, Greengard P, Nairn A, Suzuki T. Phosphorylation of the Cytoplasmic Domain of Alzheimer's β-Amyloid Precursor Protein at Ser655 by a Novel Protein Kinase. Biochemical And Biophysical Research Communications 1999, 258: 300-305. PMID: 10329382, DOI: 10.1006/bbrc.1999.0637.Peer-Reviewed Original ResearchConceptsNovel protein kinaseAlzheimer's beta-amyloid precursor proteinProtein kinase CExtracellular signal-regulated kinaseProtein kinaseCytoplasmic domainCalmodulin-dependent protein kinase IIΒ-amyloid precursor proteinPrecursor proteinAlzheimer's β-Amyloid Precursor ProteinSignal-regulated kinaseProtein kinase IIBeta-amyloid precursor proteinKinase IUnidentified proteinsKinase IIKinase CKinaseSer655ProteinAlzheimer's diseaseThr654Rat brainPhosphorylationDomainPhylogenetically 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 mechanismsKinaseProteinInhibition of the Ca2+/Calmodulin-dependent Protein Kinase I Cascade by cAMP-dependent Protein Kinase*
Matsushita M, Nairn A. Inhibition of the Ca2+/Calmodulin-dependent Protein Kinase I Cascade by cAMP-dependent Protein Kinase*. Journal Of Biological Chemistry 1999, 274: 10086-10093. PMID: 10187789, DOI: 10.1074/jbc.274.15.10086.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein Kinase KinaseCalcium-Calmodulin-Dependent Protein Kinase Type 1Calcium-Calmodulin-Dependent Protein Kinase Type 4Calcium-Calmodulin-Dependent Protein KinasesCyclic AMP-Dependent Protein KinasesFeedbackHippocampusPC12 CellsPeptide MappingPhosphorylationProtein Serine-Threonine KinasesRatsSubstrate SpecificityConceptsActivation of PKACAMP-dependent protein kinaseDependent protein kinase IProtein kinaseProtein kinase IThreonine 108Kinase ITwo-dimensional phosphopeptide mappingDependent signal transduction pathwaysInhibition of CaMKKSignal transduction pathwaysIntact PC12 cellsRegulatory phosphorylationPhosphopeptide mappingTransduction pathwaysCaMKI activityCaMKKIntact cellsPhosphorylationPC12 cellsKinaseNegative feedback mechanismEnzyme cascadeEnzyme activityRapid inhibition
1995
EF2K 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
Regulation of CFTR channel gating
Gadsby D, Nairn A. Regulation of CFTR channel gating. Trends In Biochemical Sciences 1994, 19: 513-518. PMID: 7531880, DOI: 10.1016/0968-0004(94)90141-4.Peer-Reviewed Original ResearchConceptsChannel gatingCystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channelAMP-dependent protein kinaseCFTR channel gatingReceptor-mediated activationRegulatory domainProtein kinaseATP hydrolysisCFTR channelsCl- channelsEpithelial cellsChannel openingComplex mechanismsCellsRecent advancesKinaseGenesPhosphorylationSerineGatingCFTRMutationsRegulationStemActivationIdentification 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 amplitudecGMP-dependent protein kinase regulation of a chloride channel in T84 cells
Lin M, Nairn A, Guggino S. cGMP-dependent protein kinase regulation of a chloride channel in T84 cells. American Journal Of Physiology 1992, 262: c1304-c1312. PMID: 1317106, DOI: 10.1152/ajpcell.1992.262.5.c1304.Peer-Reviewed Original ResearchConceptsProtein kinaseChloride channelsIntestinal epithelial cellsCGMP-dependent protein kinaseProtein kinase regulationApical membraneDependent protein kinaseT84 cellsEpithelial cellsInhibitor of PKGKinase regulationCatalytic subunitCombination of ATPNonhydrolyzable formExcessive fluid secretionIntracellular faceEscherichia coliElevated guanosineSingle-channel recordingsATPKinasePKGLinear current-voltage relationshipCellsChloride secretion
1991
Enhancement of the Glutamate Response by cAMP-Dependent Protein Kinase in Hippocampal Neurons
Greengard P, Jen J, Nairn A, Stevens C. Enhancement of the Glutamate Response by cAMP-Dependent Protein Kinase in Hippocampal Neurons. Science 1991, 253: 1135-1138. PMID: 1716001, DOI: 10.1126/science.1716001.Peer-Reviewed Original ResearchConceptsProtein kinaseCAMP-dependent protein kinaseGlutamate receptor channelsMonophosphate-dependent protein kinaseReceptor channelsType glutamate receptor channelsAdenylate cyclase cascadeCultured hippocampal pyramidal neuronsSpontaneous excitatory postsynaptic currentsWhole-cell current responsesSingle-channel analysisNeuromodulatory regulationMammalian brainExcitatory postsynaptic currentsHippocampal pyramidal neuronsKinaseLong-term potentiationPyramidal neuronsPostsynaptic currentsGlutamate responseExcitatory neurotransmitterMean open timeHippocampal neuronsAdenylate cyclaseSynaptic events
1989
Multisite phosphorylation of microtubule-associated protein 2 (MAP-2) in rat brain: Peptide mapping distinguishes between cyclic AMP-, calcium/calmodulin-, and calcium/phospholipid-regulated phosphorylation mechanisms
Walaas S, Nairn A. Multisite phosphorylation of microtubule-associated protein 2 (MAP-2) in rat brain: Peptide mapping distinguishes between cyclic AMP-, calcium/calmodulin-, and calcium/phospholipid-regulated phosphorylation mechanisms. Journal Of Molecular Neuroscience 1989, 1: 117-127. DOI: 10.1007/bf02918897.Peer-Reviewed Original ResearchCalcium/phospholipid-dependent protein kinasePhospholipid-dependent protein kinaseCalmodulin-dependent protein kinase IICalcium/calmodulin-dependent protein kinase IIProtein kinaseCalcium/calmodulinProtein kinase IIKinase IICyclic AMP-dependent protein kinaseAMP-dependent protein kinaseCommon phosphorylation sitesOnly serine residuesProtein 2Cyclic AMPMultisite phosphorylationThreonine residuesPhosphorylation sitesSerine residuesPhosphorylation systemPhosphorylation mechanismCytoskeletal proteinsMAP-2KinasePeptide mapsDistinct sitesChloride 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 stimulationMultisite phosphorylation of microtubule-associated protein 2 (MAP-2) in rat brain: Peptide mapping distinguishes between cyclic AMP-, calcium/calmodulin-, and calcium/phospholipid-regulated phosphorylation mechanisms
Ivar Walaas S, Nairn A. Multisite phosphorylation of microtubule-associated protein 2 (MAP-2) in rat brain: Peptide mapping distinguishes between cyclic AMP-, calcium/calmodulin-, and calcium/phospholipid-regulated phosphorylation mechanisms. Journal Of Molecular Neuroscience 1989, 1: 117-127. PMID: 2561875, DOI: 10.1007/bf02896895.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAmino AcidsAnimalsBrainCalcium-Calmodulin-Dependent Protein KinasesElectrophoresis, Gel, Two-DimensionalElectrophoresis, Polyacrylamide GelMicrotubule-Associated ProteinsOrgan SpecificityPeptide MappingPhosphopeptidesPhosphorylationProtein Kinase CProtein KinasesRatsConceptsCalcium/phospholipid-dependent protein kinasePhospholipid-dependent protein kinaseCalmodulin-dependent protein kinase IICalcium/calmodulin-dependent protein kinase IIProtein kinaseCalcium/calmodulinProtein kinase IIKinase IICyclic AMP-dependent protein kinaseAMP-dependent protein kinaseCommon phosphorylation sitesOnly serine residuesProtein 2Cyclic AMPMultisite phosphorylationThreonine residuesPhosphorylation sitesSerine residuesPhosphorylation systemPhosphorylation mechanismCytoskeletal proteinsMAP-2KinasePeptide mapsDistinct sites