2023
Mitogen-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 ResearchConceptsMitogen-activated protein kinaseSmall molecule inhibitionProtein kinaseCritical cellular functionsInhibition of PTPsProtein tyrosineCellular functionsProtein substratesPhosphorylated proteinsCell signalingTyrosine residuesAttractive therapeutic targetCellular effectsKinaseNumerous diseasesPTPDiscovery toolTherapeutic developmentTherapeutic targetMetabolic diseasesInhibitionDephosphorylationSignalingMKPProtein
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
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 ResearchConceptsNon-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 functionSignalingA 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
2013
Mitogen-Activated Protein Kinase Phosphatases in Metabolism
Lawan A, Bennett A. Mitogen-Activated Protein Kinase Phosphatases in Metabolism. 2013, 221-238. DOI: 10.1007/978-1-4614-7855-3_12.Peer-Reviewed Original ResearchMitogen-activated protein kinaseMetabolic homeostasisProtein kinaseTissue-specific mannerFamily of enzymesDirect dephosphorylationPathophysiological signalingMAPK activityMAPK inactivationMetabolic signalingImportant playersMKPHomeostasisKinaseCritical roleSignalingBody of evidenceMetabolismDephosphorylationComplex networksComparable levelsEnzymeMitogenPathwayRegulationImproved regenerative myogenesis and muscular dystrophy in mice lacking Mkp5
Shi H, Verma M, Zhang L, Dong C, Flavell RA, Bennett AM. Improved regenerative myogenesis and muscular dystrophy in mice lacking Mkp5. Journal Of Clinical Investigation 2013, 123: 2064-2077. PMID: 23543058, PMCID: PMC3635719, DOI: 10.1172/jci64375.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCrosses, GeneticDual-Specificity PhosphatasesDystrophinFemaleMaleMAP Kinase Kinase 4MAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutMuscle, SkeletalMusclesMuscular Dystrophy, DuchenneMutationP38 Mitogen-Activated Protein KinasesRegenerationStem CellsConceptsMuscle stem cell functionMitogen-activated protein kinaseStem cell functionMKP-5MAPK phosphataseSkeletal muscle diseasesRegenerative myogenesisCell functionMuscle stem cell proliferationP38 mitogen-activated protein kinaseMuscle stem cellsDegenerative skeletal muscle diseaseStem cell proliferationEssential negative regulatorProtein kinaseMuscle diseaseNegative regulatorMAPK activityGenetic lossMKP5Muscle phenotypeDystrophic muscle phenotypeStem cellsMuscular dystrophyCell proliferation
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