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
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
2017
Loss 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
Improved 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