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 ResearchMKP1 promotes nonalcoholic steatohepatitis by suppressing AMPK activity through LKB1 nuclear retention
Qiu B, Lawan A, Xirouchaki C, Yi J, Robert M, Zhang L, Brown W, Fernández-Hernando C, Yang X, Tiganis T, Bennett A. MKP1 promotes nonalcoholic steatohepatitis by suppressing AMPK activity through LKB1 nuclear retention. Nature Communications 2023, 14: 5405. PMID: 37669951, PMCID: PMC10480499, DOI: 10.1038/s41467-023-41145-5.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.PTP1BPTPMutationsSubstrateEnzymeTyrosinePathway
2022
A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK binding
Shillingford S, Zhang L, Surovtseva Y, Dorry S, Lolis E, Bennett AM. A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK binding. Journal Of Biological Chemistry 2022, 298: 102617. PMID: 36272649, PMCID: PMC9676401, DOI: 10.1016/j.jbc.2022.102617.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseP38 mitogen-activated protein kinaseMAPK bindingRegulatory mechanismsAllosteric siteMKP family membersNovel allosteric siteSmall molecule targetingMAPK/JNKAdditional regulatory mechanismsPhosphatase functionPhosphatase domainP38 MAPK/JNKProtein kinaseMKP7Site mutantsMAPK signalingAllosteric pocketMolecule targetingMAPK dephosphorylationMutantsNovel siteJNKCatalytic siteDephosphorylation
2021
MAP Kinase Phosphatase-5 Deficiency Protects Against Pressure Overload-Induced Cardiac Fibrosis
Zhong C, Min K, Zhao Z, Zhang C, Gao E, Huang Y, Zhang X, Baldini M, Roy R, Yang X, Koch WJ, Bennett AM, Yu J. MAP Kinase Phosphatase-5 Deficiency Protects Against Pressure Overload-Induced Cardiac Fibrosis. Frontiers In Immunology 2021, 12: 790511. PMID: 34992607, PMCID: PMC8724134, DOI: 10.3389/fimmu.2021.790511.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureCardiomegalyCells, CulturedDisease Models, AnimalDual-Specificity PhosphatasesEchocardiographyFibrosisHeartHeart FailureHumansInterleukin-4MacrophagesMaleMAP Kinase Signaling SystemMatrix Metalloproteinase 9MiceMice, KnockoutMyocardiumPhosphorylationPrimary Cell CultureVentricular RemodelingConceptsMitogen-activated protein kinase phosphatase 5Transverse aortic constrictionCardiac fibrosisMMP-9 expressionPressure overloadCardiac hypertrophyPressure overload-induced cardiac fibrosisOverload-induced cardiac fibrosisTAC-induced cardiac hypertrophyExcessive extracellular matrix depositionPro-fibrotic macrophagesCardiac pressure overloadP38 MAPKMatrix metalloproteinase-9Regulation of MMPsProtein kinase phosphatase 5JNK/ERKIL-4 stimulationExtracellular matrix depositionCardiac injuryAortic constrictionMyocardial fibrosisHeart diseaseFibrotic remodelingMetalloproteinase-9
2020
Tyrosyl phosphorylation of PZR promotes hypertrophic cardiomyopathy in PTPN11-associated Noonan syndrome with multiple lentigines
Yi JS, Perla S, Enyenihi L, Bennett AM. Tyrosyl phosphorylation of PZR promotes hypertrophic cardiomyopathy in PTPN11-associated Noonan syndrome with multiple lentigines. JCI Insight 2020, 5 PMID: 32584792, PMCID: PMC7455087, DOI: 10.1172/jci.insight.137753.Peer-Reviewed Original ResearchConceptsProtein tyrosine phosphataseTyrosyl phosphorylationNSML micePhosphorylation-defective mutantPTPN11 mutationsS6 kinase activityPZR tyrosyl phosphorylationTyrosine phosphataseS6 kinasePathophysiological signalingKinase activityShp2 interactionMutant fibroblastsSHP2Transmembrane glycoproteinMultiple lentiginesNoonan syndromeCraniofacial defectsPTPN11 geneHeart lysatesPhosphorylationSHP2 bindingMutationsNF-κB pathwayProtein zero
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
2017
A Phosphoproteomic Screen Identifies a Guanine Nucleotide Exchange Factor for Rab3A Protein as a Mitogen-activated Protein (MAP) Kinase Phosphatase-5-regulated MAP Kinase Target in Interleukin 6 (IL-6) Secretion and Myogenesis*
Lee H, Min K, Yi JS, Shi H, Chang W, Jackson L, Bennett AM. A Phosphoproteomic Screen Identifies a Guanine Nucleotide Exchange Factor for Rab3A Protein as a Mitogen-activated Protein (MAP) Kinase Phosphatase-5-regulated MAP Kinase Target in Interleukin 6 (IL-6) Secretion and Myogenesis*. Journal Of Biological Chemistry 2017, 292: 3581-3590. PMID: 28096466, PMCID: PMC5339744, DOI: 10.1074/jbc.m116.769208.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnimalsCell MovementCell ProliferationDual-Specificity PhosphatasesGene Expression Regulation, EnzymologicGuanine Nucleotide Exchange FactorsInterleukin-6MAP Kinase Signaling SystemMiceMice, KnockoutMuscle DevelopmentMuscle, SkeletalMutationMyoblastsPhosphorylationProteomicsRab3A GTP-Binding ProteinRegenerationSerineConceptsMitogen-activated protein kinaseMAPK phosphatase-5MAPK substratesExchange factorSer-169Guanine nucleotide exchange factorsNucleotide exchange factorsPhosphorylation-defective mutantSkeletal muscleP38 mitogen-activated protein kinaseC-Jun N-terminal kinaseMAPK-dependent signalingN-terminal kinaseSkeletal muscle functionSubstrate screenMAPK targetsSerine 169Rab3A proteinScreen identifiesRegenerative myogenesisPhosphatase 5Protein kinaseKinase targetsC2C12 myoblastsNegative regulator
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
2011
Loss of Mitogen-activated Protein Kinase Phosphatase-1 Protects from Hepatic Steatosis by Repression of Cell Death-inducing DNA Fragmentation Factor A (DFFA)-like Effector C (CIDEC)/Fat-specific Protein 27*
Flach RJ, Qin H, Zhang L, Bennett AM. Loss of Mitogen-activated Protein Kinase Phosphatase-1 Protects from Hepatic Steatosis by Repression of Cell Death-inducing DNA Fragmentation Factor A (DFFA)-like Effector C (CIDEC)/Fat-specific Protein 27*. Journal Of Biological Chemistry 2011, 286: 22195-22202. PMID: 21521693, PMCID: PMC3121364, DOI: 10.1074/jbc.m110.210237.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinase phosphatase-1Hepatic lipid homeostasisFatty acid oxidationLipid homeostasisMKP-1-deficient miceProtein kinase phosphatase-1MAPK-dependent phosphorylationFat-specific protein 27Like effector CPeroxisome proliferator-activated receptor-γ target genesProtein 27Kinase phosphatase-1Lipid droplet formationPhosphatase 1Acid oxidationLipogenic gene expressionSerine 112Target genesHepatic lipogenic gene expressionGene expressionPPARγ functionMetabolic signalsInhibitory residuesFactor AHepatic fatty acid oxidation
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
1998
Epidermal Growth Factor Receptor and the Adaptor Protein p52Shc Are Specific Substrates of T-Cell Protein Tyrosine Phosphatase
Tiganis T, Bennett A, Ravichandran K, Tonks N. Epidermal Growth Factor Receptor and the Adaptor Protein p52Shc Are Specific Substrates of T-Cell Protein Tyrosine Phosphatase. Molecular And Cellular Biology 1998, 18: 1622-1634. PMID: 9488479, PMCID: PMC108877, DOI: 10.1128/mcb.18.3.1622.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAnimalsBinding SitesCalcium-Calmodulin-Dependent Protein KinasesCell NucleusCOS CellsCytoplasmEndoplasmic ReticulumEpidermal Growth FactorErbB ReceptorsGRB2 Adaptor ProteinHeLa CellsHumansMiceMitogen-Activated Protein Kinase 1MutagenesisPhosphorylationPhosphotyrosineProtein Tyrosine Phosphatase, Non-Receptor Type 2Protein Tyrosine PhosphatasesProteinsProtein-Tyrosine KinasesShc Signaling Adaptor ProteinsSrc Homology 2 Domain-Containing, Transforming Protein 1Substrate SpecificityTyrosineConceptsT-cell protein tyrosine phosphataseSubstrate-trapping mutantEpidermal growth factor receptorProtein tyrosine phosphatasePTyr proteinsTyrosine phosphataseGrowth factor receptorPTP active siteTyrosine phosphorylated proteinsEGF-induced activationFactor receptorAlternative splicingCellular contextCOS cellsP52ShcNuclear formTC45Endoplasmic reticulumCatalytic acidSpecific substratesProteinMutantsComplex formationSpecific sitesEGF
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
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