2023
Identification of Protein Tyrosine Phosphatase (PTP) Substrates
Perla S, Qiu B, Dorry S, Yi J, Bennett A. Identification of Protein Tyrosine Phosphatase (PTP) Substrates. Methods In Molecular Biology 2023, 2743: 123-133. PMID: 38147212, DOI: 10.1007/978-1-0716-3569-8_8.Peer-Reviewed Original ResearchTeaching an old dog new tricks: A new tool for protein tyrosine phosphatase substrate discovery
Bennett A. Teaching an old dog new tricks: A new tool for protein tyrosine phosphatase substrate discovery. Journal Of Biological Chemistry 2023, 299: 104731. PMID: 37080392, PMCID: PMC10193000, DOI: 10.1016/j.jbc.2023.104731.Peer-Reviewed Original ResearchConceptsIdentification of substratesSubstrate discoveryProtein tyrosineProtein substratesInteraction networksBreast cancer cell modelsCancer cell modelsFunctional interactionNovel targetVersatile new toolNew toolCell modelComplete understandingRecent studiesOld dog new tricksNew tricksInteractorsPTP1B.PTP1BPTPMutationsSubstrateEnzymeTyrosinePathwayMitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?
Shillingford S, Bennett A. Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable? The Annual Review Of Pharmacology And Toxicology 2023, 63: 617-636. PMID: 36662585, PMCID: PMC10127142, DOI: 10.1146/annurev-pharmtox-051921-121923.Peer-Reviewed Original ResearchMeSH KeywordsHumansMitogen-Activated Protein Kinase PhosphatasesNeoplasmsProtein Tyrosine PhosphatasesSignal TransductionConceptsMitogen-activated protein kinaseSmall molecule inhibitionProtein kinaseCritical cellular functionsInhibition of PTPsProtein tyrosineCellular functionsProtein substratesPhosphorylated proteinsCell signalingTyrosine residuesAttractive therapeutic targetCellular effectsKinaseNumerous diseasesPTPDiscovery toolTherapeutic developmentTherapeutic targetMetabolic diseasesInhibitionDephosphorylationSignalingMKPProtein
2020
An allosteric site on MKP5 reveals a strategy for small-molecule inhibition
Gannam Z, Min K, Shillingford SR, Zhang L, Herrington J, Abriola L, Gareiss PC, Pantouris G, Tzouvelekis A, Kaminski N, Zhang X, Yu J, Jamali H, Ellman JA, Lolis E, Anderson KS, Bennett AM. An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling 2020, 13 PMID: 32843541, PMCID: PMC7569488, DOI: 10.1126/scisignal.aba3043.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell DifferentiationCell LineDual-Specificity PhosphatasesEnzyme InhibitorsFemaleHigh-Throughput Screening AssaysHumansKineticsMiceMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesMyoblastsProtein BindingSequence Homology, Amino AcidSignal TransductionSmall Molecule LibrariesConceptsDystrophic muscle diseaseMitogen-activated protein kinaseMuscle diseaseTGF-β1Promising therapeutic targetP38 mitogen-activated protein kinaseTherapeutic strategiesTherapeutic targetSmall molecule inhibitionSmad2 phosphorylationDiseasePotential targetSmall-molecule screenInhibitorsTreatmentInhibition
2019
Role of dual-specificity protein phosphatase DUSP10/MKP-5 in pulmonary fibrosis
Xylourgidis N, Min K, Ahangari F, Yu G, Herazo-Maya JD, Karampitsakos T, Aidinis V, Binzenhöfer L, Bouros D, Bennett AM, Kaminski N, Tzouvelekis A. Role of dual-specificity protein phosphatase DUSP10/MKP-5 in pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2019, 317: l678-l689. PMID: 31483681, PMCID: PMC6879900, DOI: 10.1152/ajplung.00264.2018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticBleomycinDual-Specificity PhosphatasesFemaleFibroblastsHumansMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesPhosphorylationPulmonary FibrosisSignal TransductionTransforming Growth Factor beta1ConceptsPulmonary fibrosisLung fibrosisFibrogenic genesLung fibroblastsM1 macrophage phenotypeIdiopathic pulmonary fibrosisHuman lung fibrosisGrowth factor-β1Levels of hydroxyprolineProtein kinase phosphatase 5IPF lungsReduced fibrosisMuscle fibrosisProfibrogenic effectsTGF-β1Smad7 levelsTherapeutic targetAnimal modelsFactor-β1FibrosisSmad3 phosphorylationEnhanced p38 MAPK activityP38 MAPK activityMyofibroblast differentiationMKP-5 expression
2018
Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function
Levy AD, Xiao X, Shaw JE, Devi S, Katrancha SM, Bennett AM, Greer CA, Howe JR, Machida K, Koleske AJ. Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function. Cell Reports 2018, 24: 1523-1535. PMID: 30089263, PMCID: PMC6234505, DOI: 10.1016/j.celrep.2018.07.006.Peer-Reviewed Original ResearchConceptsTyrosine phosphatase SHP2Noonan syndromePhosphatase SHP2Regulatory proteinsSHP2Recombinant GluN1Nck2Receptor functionNMDA receptor functionNMDAR functionGluN2B functionMutationsNMDAR dysfunctionNeuron functionNS miceGluN1ProteinAllelesNMDA receptorsDiheteromersReceptor kineticsReduced contributionsFunctionHyperactivationMice
2017
Mitogen-Activated Protein Kinase Regulation in Hepatic Metabolism
Lawan A, Bennett AM. Mitogen-Activated Protein Kinase Regulation in Hepatic Metabolism. Trends In Endocrinology And Metabolism 2017, 28: 868-878. PMID: 29128158, PMCID: PMC5774993, DOI: 10.1016/j.tem.2017.10.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 2HumansLiverMitogen-Activated Protein KinasesNon-alcoholic Fatty Liver DiseaseSignal TransductionConceptsNon-alcoholic fatty liver diseaseMitogen-activated protein kinaseHepatic metabolismLipid metabolismType 2 diabetes mellitusFatty liver diseaseHepatic mitogen-activated protein kinaseHepatic metabolic functionDiabetes mellitusLiver diseaseLiver metabolismMetabolic diseasesInsulin actionPathophysiological conditionsDiseaseMetabolismMetabolic functionsRecent insightsMellitusObesityProtein kinaseLoss of MKP-5 promotes myofiber survival by activating STAT3/Bcl-2 signaling during regenerative myogenesis
Min K, Lawan A, Bennett AM. Loss of MKP-5 promotes myofiber survival by activating STAT3/Bcl-2 signaling during regenerative myogenesis. Skeletal Muscle 2017, 7: 21. PMID: 29047406, PMCID: PMC5648478, DOI: 10.1186/s13395-017-0137-7.Peer-Reviewed Original ResearchConceptsMAPK phosphatase-5Mitogen-activated protein kinaseRegenerative myogenesisApoptotic signalingMyofiber survivalMAPK/JNK signalingMuscle regenerationSkeletal muscleP38 mitogen-activated protein kinaseMitochondrial apoptotic pathwaySkeletal muscle regenerationSkeletal muscle survivalDegenerative muscle diseasePhosphatase 5Expression of catalaseProtein kinaseSTAT3/BclSignal transducerJNK signalingWild typeExpression exhibitTranscription 3Apoptotic pathwayMitochondrial functionSignaling
2016
Low-dose dasatinib rescues cardiac function in Noonan syndrome
Yi JS, Huang Y, Kwaczala AT, Kuo IY, Ehrlich BE, Campbell SG, Giordano FJ, Bennett AM. Low-dose dasatinib rescues cardiac function in Noonan syndrome. JCI Insight 2016, 1: e90220. PMID: 27942593, PMCID: PMC5135272, DOI: 10.1172/jci.insight.90220.Peer-Reviewed Original ResearchConceptsNoonan syndromeSrc homology 2 domain-containing protein tyrosine phosphatase 2NS miceLow-dose dasatinib treatmentLow-dose dasatinibTyrosine kinase inhibitorsHearts of miceAutosomal dominant disorderCommon targetCardiac fibrosisDasatinib treatmentCardiac functionCardiomyocyte contractilityLow doseCardiac abnormalitiesShort statureNS casesNSML miceCommon autosomal dominant disorderMultiple lentiginesCraniofacial dysmorphismKinase inhibitorsMiceDasatinibProtein zero
2014
Mining the function of protein tyrosine phosphatases in health and disease
Lee H, Yi JS, Lawan A, Min K, Bennett AM. Mining the function of protein tyrosine phosphatases in health and disease. Seminars In Cell And Developmental Biology 2014, 37: 66-72. PMID: 25263013, PMCID: PMC4339398, DOI: 10.1016/j.semcdb.2014.09.021.Peer-Reviewed Original ResearchConceptsPTP functionProtein tyrosineHuman diseasesProteomic approachNon-biased approachUnanticipated roleProteomic techniquesProteomic technologiesNovel therapeutic targetPTPTherapeutic targetTyrosineFundamental cellCrucial roleHuman healthDiscoveryRegulationRoleElucidationFunctionCellsCutting-edge technologiesTarget
2001
SHP-2 complex formation with the SHP-2 substrate-1 during C2C12 myogenesis.
Kontaridis M, Liu X, Zhang L, Bennett A. SHP-2 complex formation with the SHP-2 substrate-1 during C2C12 myogenesis. Journal Of Cell Science 2001, 114: 2187-98. PMID: 11493654, DOI: 10.1242/jcs.114.11.2187.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationCell DifferentiationCell LineFibroblastsInsulinIntracellular Signaling Peptides and ProteinsMembrane GlycoproteinsMiceMitogen-Activated Protein KinasesMolecular WeightMuscle, SkeletalMyoD ProteinNeural Cell Adhesion Molecule L1Neural Cell Adhesion MoleculesP38 Mitogen-Activated Protein KinasesPhosphoproteinsPhosphorylationPhosphotyrosineProtein BindingProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesReceptors, ImmunologicSH2 Domain-Containing Protein Tyrosine PhosphatasesSignal TransductionSomatomedinsConceptsSHP-2Tyrosyl phosphorylationSH2 domain-containing tyrosine phosphataseC2C12 myoblastsSubstrate-1MyoD-responsive genesMitogen-activated protein kinase activityP38 mitogen-activated protein kinase activityMuscle-specific genesProtein tyrosine kinasesSkeletal muscle differentiationProtein kinase activityExpression of MyoD.Cell-cell recognitionComplex formationInvolvement of tyrosineTyrosine phosphataseGab-1C2C12 myogenesisMuscle differentiationBinder 1Kinase activityInducible activationMyoD expressionTyrosine kinase
2000
Differential Role of β1C and β1AIntegrin Cytoplasmic Variants in Modulating Focal Adhesion Kinase, Protein Kinase B/AKT, and Ras/Mitogen-activated Protein Kinase Pathways
Fornaro M, Steger C, Bennett A, Wu J, Languino L. Differential Role of β1C and β1AIntegrin Cytoplasmic Variants in Modulating Focal Adhesion Kinase, Protein Kinase B/AKT, and Ras/Mitogen-activated Protein Kinase Pathways. Molecular Biology Of The Cell 2000, 11: 2235-2249. PMID: 10888665, PMCID: PMC14916, DOI: 10.1091/mbc.11.7.2235.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionCHO CellsCricetinaeCytoplasmEnzyme ActivationFibronectinsFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesGene ExpressionHumansIntegrin beta1IntegrinsMitogen-Activated Protein Kinase 1PhosphorylationProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRabbitsRas ProteinsSignal TransductionConceptsStable cell linesMAP kinase pathwayKinase pathwayRas activationERK2 activationRas/MAP kinase pathwayCell proliferationProtein kinase B/Akt activitySurvival signalsProtein kinase B/AktRas/mitogen-activated protein kinase pathwayExtracellular signal-regulated kinase 2 activationCell linesProtein kinase B/Akt phosphorylationMitogen-activated protein kinase pathwayFocal adhesion kinase phosphorylationUnique signaling mechanismVariant cytoplasmic domainKinase 2 activationFocal adhesion kinaseProtein kinase pathwayModulates cell proliferationMAPK kinaseCytoplasmic domainAdhesion kinase
1997
Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein Kinases
Bennett A, Tonks N. Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein Kinases. Science 1997, 278: 1288-1291. PMID: 9360925, DOI: 10.1126/science.278.5341.1288.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein KinasesCell Cycle ProteinsCell DifferentiationCell DivisionCell LineCloning, MolecularCulture MediaCyclin D1Dual Specificity Phosphatase 1Gene Expression Regulation, DevelopmentalImmediate-Early ProteinsJNK Mitogen-Activated Protein KinasesMiceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein KinasesMitogensMuscle ProteinsMuscle, SkeletalPhosphoprotein PhosphatasesPhosphorylationProtein Phosphatase 1Protein Tyrosine PhosphatasesRecombinant Fusion ProteinsSignal TransductionTetracyclineTranscription, GeneticConceptsMuscle-specific gene expressionMAPK phosphatase-1Skeletal muscle differentiationMuscle differentiationGene expressionMitogen-Activated Protein KinaseMuscle-specific genesSignal transduction pathwaysMKP-1 overexpressionPhosphatase 1Extracellular signalsProtein kinaseTransduction pathwaysMitogen withdrawalC2C12 myoblastsDifferentiated myocytesMyotube formationEndogenous expressionMyosin heavy chainMyogenesisDifferentiationHeavy chainExpressionOverexpressionAppropriate expression
1995
Different Signaling Roles of SHPTP2 in Insulin-induced GLUT1 Expression and GLUT4 Translocation ∗
Hausdorff S, Bennett A, Neel B, Birnbaum M. Different Signaling Roles of SHPTP2 in Insulin-induced GLUT1 Expression and GLUT4 Translocation ∗. Journal Of Biological Chemistry 1995, 270: 12965-12968. PMID: 7768884, DOI: 10.1074/jbc.270.22.12965.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsBase SequenceBiological TransportDNA PrimersGlucose Transporter Type 1Glucose Transporter Type 4InsulinIntracellular Signaling Peptides and ProteinsMiceMicroinjectionsMolecular Sequence DataMonosaccharide Transport ProteinsMuscle ProteinsProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesRNA, MessengerSignal TransductionConceptsGLUT4 translocationNon-transmembrane protein tyrosine phosphataseSrc homology 2 domainGlutathione S-transferase fusion proteinS-transferase fusion proteinC-terminal SH2 domainCell surface GLUT1Insulin receptor substrate-1Cell surfaceProtein tyrosine phosphataseInsulin-stimulated mitogenesisTranslocation of GLUT4Insulin-stimulated expressionReceptor substrate-1Insulin-induced DNA synthesisInsulin-stimulated increaseNIH 3T3 fibroblastsSH2 domainSHPTP2Signaling roleSubstrate-1Fusion proteinInsulin stimulationMetabolic pathwaysIndependent pathways
1994
Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras.
Bennett A, Tang T, Sugimoto S, Walsh C, Neel B. Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 7335-7339. PMID: 8041791, PMCID: PMC44394, DOI: 10.1073/pnas.91.15.7335.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsBase SequenceBinding SitesCell LineDNAGenes, rasHumansIntracellular Signaling Peptides and ProteinsMiceMice, Inbred BALB CMolecular Sequence DataPhosphorylationProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesReceptors, Platelet-Derived Growth FactorSH2 Domain-Containing Protein Tyrosine PhosphatasesSignal TransductionConceptsPlatelet-derived growth factor receptor betaGrowth factor receptor betaPDGF stimulationPositive signalingReceptor tyrosine kinasesSH2 domainRas activationGrowth factor receptorReceptor betaTyrosine phosphorylationSHPTP2Gene productsTyrosine kinaseGrb2Vivo sitesFactor receptorPhosphorylationSignalingPositive signalsSOS1RAHomologuesKinaseSite displayBeta