2010
Deciphering Protein Kinase Specificity Through Large-Scale Analysis of Yeast Phosphorylation Site Motifs
Mok J, Kim PM, Lam HY, Piccirillo S, Zhou X, Jeschke GR, Sheridan DL, Parker SA, Desai V, Jwa M, Cameroni E, Niu H, Good M, Remenyi A, Nianhan J, Sheu YJ, Sassi HE, Sopko R, Chan CS, De Virgilio C, Hollingsworth NM, Lim WA, Stern DF, Stillman B, Andrews BJ, Gerstein MB, Snyder M, Turk BE. Deciphering Protein Kinase Specificity Through Large-Scale Analysis of Yeast Phosphorylation Site Motifs. Science Signaling 2010, 3: ra12. PMID: 20159853, PMCID: PMC2846625, DOI: 10.1126/scisignal.2000482.Peer-Reviewed Original ResearchConceptsPhosphorylation site motifsSite motifShort linear sequence motifsKinase substrate recognitionKinase-substrate relationshipsProtein kinase specificityKinase catalytic domainLinear sequence motifsPrediction of thousandsCMGC groupKinase specificityPhosphorylation targetsKinase substrateYeast proteomeSequence motifsSubstrate recognitionKinase familyProtein substratesCatalytic domainProtein kinaseLarge-scale analysisPrimary sequenceCandidate substratesComputational scanningKinase
2006
Global Analysis of Protein Phosphorylation in Yeast
Ptacek J, Devgan G, Michaud G, Zhu H, Zhu X, Fasolo J, Guo H, Jona G, Breitkreutz A, Sopko R, McCartney R, Schmidt M, Rachidi N, Lee S, Mah A, Meng L, Stark M, Stern D, De Virgilio C, Tyers M, Andrews B, Gerstein M, Schweitzer B, Predki P, Snyder M. Global Analysis of Protein Phosphorylation in Yeast. The FASEB Journal 2006, 20: a1308-a1308. DOI: 10.1096/fasebj.20.5.a1308.Peer-Reviewed Original ResearchProtein phosphorylationProtein kinaseNovel regulatory moduleDifferent biochemical functionsNumber of kinasesMajor regulatory mechanismSame cellular compartmentSame functional categoryYeast kinasesCellular rolesCyclin subunitPhosphorylation eventsRegulatory modulesYeast proteinsVivo substratePhosphorylation resultsBiochemical functionsRelated kinasesTranscription factorsCellular compartmentsFunctional categoriesBiochemical understandingRegulatory mechanismsDifferent proteinsKinase
2005
Activation of the Checkpoint Kinase Rad53 by the Phosphatidyl Inositol Kinase-like Kinase Mec1*
Ma JL, Lee SJ, Duong JK, Stern DF. Activation of the Checkpoint Kinase Rad53 by the Phosphatidyl Inositol Kinase-like Kinase Mec1*. Journal Of Biological Chemistry 2005, 281: 3954-3963. PMID: 16365046, DOI: 10.1074/jbc.m507508200.Peer-Reviewed Original ResearchConceptsPhosphorylation-dependent mechanismDNA damageKinase activityDNA replication checkpoint pathwayRad53 kinase activityCheckpoint kinase Rad53Essential protein kinaseReplication checkpoint pathwayActivation of Rad53Protein kinase activityMammalian Chk2Rad53 phosphorylationRad53 activationRad53Protein kinaseDownstream responsesCheckpoint pathwayOrthologsAutophosphorylationKinasePhosphorylationIntermolecular mechanismActivationPIKKsComplexesGlobal analysis of protein phosphorylation in yeast
Ptacek J, Devgan G, Michaud G, Zhu H, Zhu X, Fasolo J, Guo H, Jona G, Breitkreutz A, Sopko R, McCartney RR, Schmidt MC, Rachidi N, Lee SJ, Mah AS, Meng L, Stark MJ, Stern DF, De Virgilio C, Tyers M, Andrews B, Gerstein M, Schweitzer B, Predki PF, Snyder M. Global analysis of protein phosphorylation in yeast. Nature 2005, 438: 679-684. PMID: 16319894, DOI: 10.1038/nature04187.Peer-Reviewed Original ResearchConceptsProtein phosphorylationBasic cellular processesGlobal phosphorylation networksFirst-generation mapYeast kinasesPhosphorylation networksYeast proteinsCellular processesPhosphorylationKinaseYeastSearchable formatGlobal analysisProteinPrime targetEukaryotesNew resourcesProteomicsOrganismsRegulationPathwayChip technologyTargetDNA Damage Regulates Chk2 Association with Chromatin*
Li J, Stern DF. DNA Damage Regulates Chk2 Association with Chromatin*. Journal Of Biological Chemistry 2005, 280: 37948-37956. PMID: 16150728, DOI: 10.1074/jbc.m509299200.Peer-Reviewed Original ResearchConceptsChromatin-enriched fractionDNA damageATM-dependent mannerUpstream phosphatidylinositolPresence of ATPChromatin fractionationDNA repairHypophosphorylated formEffector substratesChk2Hyperphosphorylated formsChromatinCell cyclePhosphorylated formCluster domainDiverse responsesArtificial inductionSoluble substratesCritical mediatorSmall poolSoluble fractionCdc25APhosphatidylinositolKinaseTransmit signalPhosphoproteomics for oncology discovery and treatment
Stern DF. Phosphoproteomics for oncology discovery and treatment. Expert Opinion On Therapeutic Targets 2005, 9: 851-860. PMID: 16083347, DOI: 10.1517/14728222.9.4.851.Peer-Reviewed Original ResearchConceptsPhosphoproteomic analysisProtein phosphorylationReversible protein phosphorylationSignal transduction pathwaysCellular regulationProtein kinaseTransduction pathwaysHuman cancersDevelopment of drugsPathwayPhosphorylationGood targetImportant insightsCancer therapyCancer drugsPhosphoproteomicsCellsIndividual tumorsPowerful toolKinaseRegulationIntermediary levelDiscoveryTargetIdentificationThe Plk1 Polo Box Domain Mediates a Cell Cycle and DNA Damage Regulated Interaction with Chk2
Tsvetkov LM, Tsekova RT, Xu X, Stern DF. The Plk1 Polo Box Domain Mediates a Cell Cycle and DNA Damage Regulated Interaction with Chk2. Cell Cycle 2005, 4: 602-610. PMID: 15876876, DOI: 10.4161/cc.4.4.1599.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCatalytic DomainCell CycleCell Cycle ProteinsCell DivisionCell SeparationCheckpoint Kinase 2DNA DamageDNA RepairG2 PhaseGenetic VectorsGlutathione TransferaseHeLa CellsHumansImmunoblottingImmunoprecipitationIn Vitro TechniquesMitosisPhosphorylationProtein BindingProtein KinasesProtein Serine-Threonine KinasesProtein Structure, TertiaryProto-Oncogene ProteinsSignal TransductionConceptsPlk1 polo-box domainDNA damage checkpointPolo-box domainPolo-like kinase 1Eukaryotic proteinsDamage checkpointMitotic regulationBox domainRegulated interactionPlk1 activityProtein kinaseSignaling cascadesChk2Kinase 1Tumor suppressorCell cycleDNA damageS phasePlk1M phaseMitosisMultiple processesPotential mechanismsPhosphorylatesKinase
2004
Establishment of a Cell-Free System to Study the Activation of Chk2
Xu X, Stern DF. Establishment of a Cell-Free System to Study the Activation of Chk2. Methods In Molecular Biology 2004, 280: 165-174. PMID: 15187252, DOI: 10.1385/1-59259-788-2:165.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell-Free SystemCheckpoint Kinase 2DNA DamageDNA-Binding ProteinsGenetic VectorsHumansImmunoblottingPlasmidsPrecipitin TestsProtein BiosynthesisProtein Serine-Threonine KinasesRabbitsReticulocytesTranscription, GeneticTriticumTumor Suppressor ProteinsConceptsActivation of Chk2Cell-free systemVitro transcription/translation systemTranscription/translation systemCheckpoint kinase Chk2Rabbit reticulocyte lysateWheat germ extractKinase Chk2Identification of cofactorsReticulocyte lysateChk2Germ extractDNA damageTranslation systemActivationKinaseCofactorProteinATRLysatesPathway
2000
Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases
Stern D. Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases. Breast Cancer Research 2000, 2: 176. PMID: 11250707, PMCID: PMC138772, DOI: 10.1186/bcr51.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiomarkersBreast NeoplasmsEpidermal Growth FactorErbB ReceptorsFemaleGene AmplificationGene Expression Regulation, DevelopmentalGene Expression Regulation, NeoplasticGenes, erbBHumansProtein-Tyrosine KinasesReceptor, ErbB-2Signal TransductionTranscriptional ActivationTransforming Growth FactorsTrastuzumabConceptsBreast cancerErbB family receptor tyrosine kinasesReceptor tyrosine kinasesHER2/neuTyrosine kinaseEpidermal growth factor receptorGrowth factor receptorClinical trialsSteroid receptorsTherapeutic antibodiesErbB-2Factor receptorReceptorsCancerPhysiological regulatorSignificant subsetFamily membersKinaseOptimal useNeuHormoneTrialsAntibodiesHerceptin
1998
Rad53 FHA Domain Associated with Phosphorylated Rad9 in the DNA Damage Checkpoint
Sun Z, Hsiao J, Fay D, Stern D. Rad53 FHA Domain Associated with Phosphorylated Rad9 in the DNA Damage Checkpoint. Science 1998, 281: 272-274. PMID: 9657725, DOI: 10.1126/science.281.5374.272.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell Cycle ProteinsCheckpoint Kinase 2DNA DamageDNA ReplicationFungal ProteinsG2 PhaseHydroxyureaMethyl MethanesulfonateMitosisMutationOligopeptidesPeptidesPhosphorylationProtein KinasesProtein Serine-Threonine KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscription, GeneticConceptsRad53 phosphorylationRad53 protein kinaseDNA damage signalsDNA damage checkpointProtein-binding domainsCell cycle phase arrestRNR3 transcriptionRad9 proteinFHA domainDamage checkpointG2/M cell cycle phase arrestCell divisionProtein kinaseSaccharomyces cerevisiaeDamage signalsRad9DNA damageRad53Phase arrestPhosphorylationCheckpointDomainCerevisiaeTranscriptionKinase
1997
Dimerization of the p185neu transmembrane domain is necessary but not sufficient for transformation
Burke C, Lemmon M, Coren B, Engelman D, Stern D. Dimerization of the p185neu transmembrane domain is necessary but not sufficient for transformation. Oncogene 1997, 14: 687-696. PMID: 9038376, DOI: 10.1038/sj.onc.1200873.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesTransmembrane domainEpidermal growth factor receptorSignal transductionWild-type domainSecond-site mutationsPosition 664Dimerization domainGrowth factor receptorTyrosine kinaseGlycophorin AFactor receptorValine substitutionDimerizationMutationsTransductionGlutamic acidDomainWeak dimerizationMutantsKinaseSignalingProteinEGFChimerasMutations in SPK1/RAD53 that specifically abolish checkpoint but not growth-related functions
Fay DS, Sun Z, Stern D. Mutations in SPK1/RAD53 that specifically abolish checkpoint but not growth-related functions. Current Genetics 1997, 31: 97-105. PMID: 9021124, DOI: 10.1007/s002940050181.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCell Cycle ProteinsCheckpoint Kinase 2Cloning, MolecularElectrophoresis, Polyacrylamide GelGene Expression Regulation, EnzymologicGene Expression Regulation, FungalMutagenesisPlasmidsProtein KinasesProtein Serine-Threonine KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence DeletionTransformation, GeneticConceptsCheckpoint functionKinase domainKinase activityEssential protein kinaseWild-type levelsGrowth-related functionsCheckpoint arrestProtein kinaseDeletional analysisN-terminusSPK1Cell cycleMutant allelesGrowth activityMutationsRad53Normal rateSaccharomycesMultiple stagesKinaseDomainCheckpointActivityAllelesRegulation
1996
Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways.
Sun Z, Fay DS, Marini F, Foiani M, Stern DF. Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways. Genes & Development 1996, 10: 395-406. PMID: 8600024, DOI: 10.1101/gad.10.4.395.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseCell CycleCell Cycle ProteinsCell DivisionCheckpoint Kinase 2DNA DamageDNA ReplicationDNA, FungalFungal ProteinsGene Expression Regulation, FungalGenes, FungalHydroxyureaImmunoblottingIntracellular Signaling Peptides and ProteinsMethyl MethanesulfonateMutagenesisPhosphorylationPrecipitin TestsProtein KinasesProtein Serine-Threonine KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSignal TransductionTemperatureConceptsProtein kinaseCheckpoint pathwayEssential protein kinaseDamage checkpoint pathwayDamage-induced phosphorylationKinase-defective formG1/S boundarySignal transduction pathwaysRegulation of phosphorylationTreatment of cellsCheckpoint functionCdc mutantsDNA replicationProtein phosphorylationUpstream kinaseCheckpoint arrestRegulated phosphorylationTransduction pathwaysKinase activityCell cyclePhosphorylationS boundaryDamage DNACycle arrestKinase
1995
ScSpk1 Spk1 (S. cerevisiae)
Zheng P, Fay D, Stern D. ScSpk1 Spk1 (S. cerevisiae). 1995, 126-127. DOI: 10.1016/b978-012324719-3/50028-5.Peer-Reviewed Original ResearchKinase domainProtein kinaseMluI cell cycle boxS-phase-specific genesS phase-specific expressionPhase-specific genesPhase-specific expressionTyr kinase activitySer/ThrSpecific protein kinasesProtein tyrosine kinasesTranscriptional regulationMutant cellsNuclear proteinsNuclear localizationKinase activitySPK1DNA damageKinaseDNA synthesisProteinRepair synthesisGenesLatter activityImportant role
1989
The Ick tyrosine protein kinase interacts with the cytoplasmic tail of the CD4 glycoprotein through its unique amino-terminal domain
Shaw A, Amrein K, Hammond C, Stern D, Sefton B, Rose J. The Ick tyrosine protein kinase interacts with the cytoplasmic tail of the CD4 glycoprotein through its unique amino-terminal domain. Cell 1989, 59: 627-636. PMID: 2582490, DOI: 10.1016/0092-8674(89)90008-1.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBase SequenceCD4 AntigensCytoplasmHeLa CellsHumansLymphocyte Specific Protein Tyrosine Kinase p56(lck)Macromolecular SubstancesMembrane GlycoproteinsMolecular Sequence DataMutationOligonucleotide ProbesPhosphoproteinsPlasmidsProtein BindingProtein MultimerizationProtein-Tyrosine KinasesT-LymphocytesTransfectionConceptsAmino-terminal domainCytoplasmic domainTyrosine protein kinase p56lckUnique amino-terminal domainT cell-specific proteinsTyrosine protein kinaseSpecific transmembrane proteinsCell-specific proteinsIntracellular tyrosine kinaseAmino-terminal residuesCarboxy-terminal residuesTransmembrane proteinCytoplasmic tailSrc familyProtein kinaseKinase p56lckTyrosine kinaseHeLa cellsCell surfaceProteinDeleted formsSurface glycoproteinP56lckKinaseResidues