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
A feed-forward regulatory loop in adipose tissue promotes signaling by the hepatokine FGF21
Han MS, Perry RJ, Camporez JP, Scherer PE, Shulman GI, Gao G, Davis RJ. A feed-forward regulatory loop in adipose tissue promotes signaling by the hepatokine FGF21. Genes & Development 2020, 35: 133-146. PMID: 33334822, PMCID: PMC7778269, DOI: 10.1101/gad.344556.120.Peer-Reviewed Original Research
2018
Activation of RhoA, Smad2, c‐Src, PKC‐βII/δ and JNK in atopic dermatitis
Lu J, Yin R, Fu Z, Lee V, Nelson J, Tan W. Activation of RhoA, Smad2, c‐Src, PKC‐βII/δ and JNK in atopic dermatitis. Australasian Journal Of Dermatology 2018, 59: e258-e261. PMID: 29498756, PMCID: PMC6978706, DOI: 10.1111/ajd.12801.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedDermatitis, AtopicDermisEpidermisFemaleHumansJNK Mitogen-Activated Protein KinasesMaleMiddle AgedPhosphorylationProtein Kinase C betaReceptor, Transforming Growth Factor-beta Type IrhoA GTP-Binding ProteinSeverity of Illness IndexSmad2 Proteinsrc-Family KinasesUp-RegulationYoung AdultConceptsExpression of TGFβR1Atopic dermatitisAtopic dermatitis severityInfiltrated inflammatory cellsMultifactorial skin diseaseActivation of Smad2C-SrcDermatitis severityInflammatory progressionInflammatory cellsSkin diseasesActivation of RhoAPhosphorylation levelsDermatitisTGFβR1JNKSmad2ActivationInflammationChronicPathogenesisExpressionRhoADiseaseProgression
2015
A TPL2 (MAP3K8) disease-risk polymorphism increases TPL2 expression thereby leading to increased pattern recognition receptor-initiated caspase-1 and caspase-8 activation, signalling and cytokine secretion
Hedl M, Abraham C. A TPL2 (MAP3K8) disease-risk polymorphism increases TPL2 expression thereby leading to increased pattern recognition receptor-initiated caspase-1 and caspase-8 activation, signalling and cytokine secretion. Gut 2015, 65: 1799. PMID: 26215868, PMCID: PMC5106344, DOI: 10.1136/gutjnl-2014-308922.Peer-Reviewed Original ResearchConceptsCaspase-8 activationMonocyte-derived macrophagesAutocrine IL-1βIL-18 secretionHost-microbial interactionsCytokine secretionHuman monocyte-derived macrophagesHuman myeloid cellsMyeloid cellsCaspase-1Intestinal myeloid cellsPattern recognition receptorsOligomerisation domainIL-1βPrimary human myeloid cellsReal-time PCRFunctional consequencesTpl2NFκB signalingRecognition receptorsRNA expressionIntestinal immune homeostasisERKMyeloid-derived cellsJNK
2014
Regulation of hepatic insulin receptor activity following injury
Jiang S, Gavrikova T, Messina J. Regulation of hepatic insulin receptor activity following injury. AJP Gastrointestinal And Liver Physiology 2014, 306: g886-g892. PMID: 24699331, PMCID: PMC4024725, DOI: 10.1152/ajpgi.00128.2013.Peer-Reviewed Original ResearchConceptsImpaired insulin receptorO-GlcNAc modificationO-GlcNAcIR tyrosine phosphorylationIR protein levelsInvolvement of JNKInhibition of JNKInsulin receptor activationIncreased serine phosphorylationTyrosine phosphorylationSer/Thr residuesPosttranslational modificationsSerine phosphorylationMembrane localizationIR activityInsulin receptorModel of insulin resistancePhosphorylationSer/ThrJNKTyrosine nitrationProtein levelsModels of injuryType 2 diabetesIR function
2012
Both Internalization and AIP1 Association Are Required for Tumor Necrosis Factor Receptor 2-Mediated JNK Signaling
Ji W, Li Y, Wan T, Wang J, Zhang H, Chen H, Min W. Both Internalization and AIP1 Association Are Required for Tumor Necrosis Factor Receptor 2-Mediated JNK Signaling. Arteriosclerosis Thrombosis And Vascular Biology 2012, 32: 2271-2279. PMID: 22743059, PMCID: PMC3421067, DOI: 10.1161/atvbaha.112.253666.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBinding SitesCells, CulturedEndothelial CellsEnzyme ActivationHuman Umbilical Vein Endothelial CellsHumansJNK Mitogen-Activated Protein KinasesMiceMice, KnockoutNF-kappa BProtein Interaction Domains and MotifsProtein Transportras GTPase-Activating ProteinsReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IISequence DeletionSignal TransductionTime FactorsTNF Receptor-Associated Factor 2TransfectionTumor Necrosis Factor-alphaConceptsJNK signalingApoptotic signalingJNK activationDomain IICaspase-dependent cell deathCell deathTNF receptor 1C-Jun N-terminal kinaseDependent cell survivalN-terminal kinaseNF-κB activationNF-κBDeletion analysisTNF responseLL motifPlasma membraneIntracellular regionCell survivalDomain IJNKSignalingDistinct rolesTNFR2 deletionProtein 1Specific deletion
2011
MEKK3 Regulates IFN-γ Production in T Cells through the Rac1/2-Dependent MAPK Cascades
Wang X, Zhang F, Chen F, Liu D, Zheng Y, Zhang Y, Dong C, Su B. MEKK3 Regulates IFN-γ Production in T Cells through the Rac1/2-Dependent MAPK Cascades. The Journal Of Immunology 2011, 186: 5791-5800. PMID: 21471448, PMCID: PMC3833674, DOI: 10.4049/jimmunol.1002127.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAminoquinolinesAnimalsCD4-Positive T-LymphocytesCell LineFlow CytometryImmunoblottingInterferon-gammaInterleukin-12Interleukin-18Listeria monocytogenesMAP Kinase Kinase Kinase 3MAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein KinasesPyrimidinesrac GTP-Binding Proteinsrac1 GTP-Binding ProteinReceptors, Antigen, T-CellConceptsSer/Thr proteinMAPK activationMAPK kinase kinase (MAP3K) familyP38 MAPK activationThr proteinMAPK cascadeKinase familyMAPK signalsConditional knockout miceMEKK3 activationMEKK3 deficiencyMEKK3Cell differentiationTCR stimulationTCR signalsTh2 cell differentiationSpecific roleBacterial infectionsT cellsCellsKnockout miceActivationJNKProductionProtein
2010
Activation of JNK signaling links lgl mutations to disruption of the cell polarity and epithelial organization in Drosophila imaginal discs
Zhu M, Xin T, Weng S, Gao Y, Zhang Y, Li Q, Li M. Activation of JNK signaling links lgl mutations to disruption of the cell polarity and epithelial organization in Drosophila imaginal discs. Cell Research 2010, 20: 242-245. PMID: 20066009, DOI: 10.1038/cr.2010.2.Peer-Reviewed Original Research
2009
The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow
Hahn C, Orr AW, Sanders JM, Jhaveri KA, Schwartz MA. The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow. Circulation Research 2009, 104: 995-1003. PMID: 19286608, PMCID: PMC2702158, DOI: 10.1161/circresaha.108.186486.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins EAtherosclerosisBasement MembraneCattleCell Culture TechniquesCells, CulturedCollagenDisease Models, AnimalEndothelial CellsEnzyme ActivationExtracellular MatrixFibronectinsHemorheologyInflammationIntegrinsJNK Mitogen-Activated Protein KinasesMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase KinasesOscillometryp21-Activated KinasesPhosphorylationRegional Blood FlowStress, Mechanical
2006
Varicella-Zoster Virus Infection of Human Fibroblast Cells Activates the c-Jun N-Terminal Kinase Pathway
Zapata HJ, Nakatsugawa M, Moffat JF. Varicella-Zoster Virus Infection of Human Fibroblast Cells Activates the c-Jun N-Terminal Kinase Pathway. Journal Of Virology 2006, 81: 977-990. PMID: 17079291, PMCID: PMC1797429, DOI: 10.1128/jvi.01470-06.Peer-Reviewed Original ResearchConceptsPhospho-c-JunC-JunPhospho-JNKKinase pathwayC-Jun N-terminal kinaseC-Jun N-terminal kinase (JNK) pathwayTranscription factor ATF-2N-terminal kinase pathwayProtein kinase pathwayImmunofluorescent confocal microscopyN-terminal kinaseBiochemical fractionationKinase assaysUseful drug targetC-Jun levelsATF-2Phosphorylated formVirus genesJNK pathwayDrug targetsHuman fibroblast cellsPhosphorylated JNKJNKMain activatorHuman foreskin fibroblasts
2005
Molecular mechanism(s) of burn-induced insulin resistance in murine skeletal muscle: Role of IRS phosphorylation
Zhang Q, Carter E, Ma B, White M, Fischman A, Tompkins R. Molecular mechanism(s) of burn-induced insulin resistance in murine skeletal muscle: Role of IRS phosphorylation. Life Sciences 2005, 77: 3068-3077. PMID: 15982669, DOI: 10.1016/j.lfs.2005.02.034.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBurnsDisease Models, AnimalEnzyme ActivationHindlimbInsulin Receptor Substrate ProteinsInsulin ResistanceJNK Mitogen-Activated Protein KinasesMaleMAP Kinase Kinase 4MiceMitogen-Activated Protein Kinase KinasesMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionConceptsInsulin receptor substrate-1Burn-induced insulin resistanceAkt kinase activityIRS-1 proteinSAPK/JNKSerine 307Kinase activitySkeletal muscleReceptor substrate-1Murine skeletal muscleHind limb skeletal muscleStress kinasesKey proteinsSubstrate-1Biochemical basisPhosphorylationIRS phosphorylationKinase enzymeProteinEnzyme activityJNKLimb skeletal muscleProtein contentInsulin resistanceKinaseIntegrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch*
Katsumi A, Naoe T, Matsushita T, Kaibuchi K, Schwartz MA. Integrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch*. Journal Of Biological Chemistry 2005, 280: 16546-16549. PMID: 15760908, DOI: 10.1074/jbc.c400455200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionEnzyme ActivationEnzyme InhibitorsExtracellular MatrixExtracellular Signal-Regulated MAP KinasesIntegrin alphaVbeta3IntegrinsJNK Mitogen-Activated Protein KinasesLigandsMAP Kinase Kinase 4MiceMitogen-Activated Protein Kinase KinasesNIH 3T3 CellsPhosphatidylinositol 3-KinasesPhosphorylationProtein ConformationSignal TransductionStress, MechanicalTime FactorsConceptsIntegrin activationExtracellular matrix proteinsRole of integrinsConformational activationBiochemical signalsNIH3T3 cellsMolecular mechanismsCellular responsesMatrix proteinsExtracellular matrixCell growthMechanical stretch stimulationIntegrin alphavbeta3IntegrinsMechanical tensionMechanical stretchCritical determinantStretch stimulationActivationPhosphoinositolMechanotransductionJNKProteinApoptosisDifferentiation
2004
JNK activation is critical for Aplidin™-induced apoptosis
Cuadrado A, González L, Suárez Y, Martínez T, Muñoz A. JNK activation is critical for Aplidin™-induced apoptosis. Oncogene 2004, 23: 4673-4680. PMID: 15122339, DOI: 10.1038/sj.onc.1207636.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsApoptosisBlotting, WesternBreast NeoplasmsCell DivisionCell Line, TumorCell SurvivalDepsipeptidesEnzyme ActivationFemaleFibroblastsHumansMitogen-Activated Protein KinasesNF-kappa BPeptides, CyclicPhosphorylationPrecipitin TestsProto-Oncogene Proteins c-junTranscription Factor AP-1Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylation
Carlson C, White M, Rondinone C. Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylation. Biochemical And Biophysical Research Communications 2004, 316: 533-539. PMID: 15020250, DOI: 10.1016/j.bbrc.2004.02.082.Peer-Reviewed Original ResearchConceptsSerine 307 phosphorylationSerine 307Rapamycin-sensitive mannerInsulin receptor substrateRole of mTORAmino acid stimulationActivation of mTORPhosphatase PP2AKinase mTOROkadaic acidReceptor substrateInsulin signalingIRS-1MTOR activityPhosphorylationMammalian targetMTORCytosolic fractionRapamycinPP2AAcid stimulationPKBInhibitorsSignalingJNK
2001
Requirement of the JIP1 scaffold protein for stress-induced JNK activation
Whitmarsh A, Kuan C, Kennedy N, Kelkar N, Haydar T, Mordes J, Appel M, Rossini A, Jones S, Flavell R, Rakic P, Davis R. Requirement of the JIP1 scaffold protein for stress-induced JNK activation. Genes & Development 2001, 15: 2421-2432. PMID: 11562351, PMCID: PMC312784, DOI: 10.1101/gad.922801.Peer-Reviewed Original ResearchConceptsJIP1 scaffold proteinSignal transduction pathwaysScaffold proteinTransduction pathwaysMAP kinase signal transduction pathwayJNK activationStress-induced JNK activationKinase signal transduction pathwayC-Jun N-terminal kinase (JNK) signal transduction pathwayExposure of cellsHomologous recombinationEnvironmental stressPrimary hippocampal neuronsC-JunAnoxic stressJIP1ProteinPathwayJNKExcitotoxic stressHippocampal neuronsActivationGenesStressCritical component
2000
The c-Jun NH2-terminal Kinase Promotes Insulin Resistance during Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307 *
Davis R, Aguirre V, Uchida T, Yenush L, White M. The c-Jun NH2-terminal Kinase Promotes Insulin Resistance during Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307 *. Journal Of Biological Chemistry 2000, 275: 9047-9054. PMID: 10722755, DOI: 10.1074/jbc.275.12.9047.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnisomycinCHO CellsCricetinaeHumansInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceJNK Mitogen-Activated Protein KinasesMiceMitogen-Activated Protein KinasesMolecular Sequence DataPhosphoproteinsPhosphorylationProtein BindingReceptor, InsulinRecombinant ProteinsSerineSignal TransductionTumor Necrosis Factor-alphaConceptsInsulin-stimulated tyrosine phosphorylationIRS-1Serine 307Tyrosine phosphorylationInsulin receptor substrate-1IRS-1 functionSignal transduction cascadePhosphorylation of Ser307Receptor substrate-1Chinese hamster ovary cellsIRS proteinsActivity of JNKJNK associatesPhosphorylation sitesHamster ovary cellsTransduction cascadeSerine phosphorylationTerminal kinaseSubstrate-1PhosphorylationStrong activatorPromotes Insulin ResistanceJNK phosphorylationOvary cellsJNK
1998
YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage TNF‐α production and downregulation of the MAP kinases p38 and JNK
Palmer L, Hobbie S, Galán J, Bliska J. YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage TNF‐α production and downregulation of the MAP kinases p38 and JNK. Molecular Microbiology 1998, 27: 953-965. PMID: 9535085, DOI: 10.1046/j.1365-2958.1998.00740.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial Outer Membrane ProteinsCalcium-Calmodulin-Dependent Protein KinasesCell LineCloning, MolecularDown-RegulationEnzyme ActivationGene Expression Regulation, BacterialGenetic Complementation TestImmunoblottingJNK Mitogen-Activated Protein KinasesLipopolysaccharidesMacrophagesMiceMitogen-Activated Protein KinasesMutationp38 Mitogen-Activated Protein KinasesTumor Necrosis Factor-alphaYersinia pseudotuberculosisConceptsY. pseudotuberculosisTNF-alpha productionMitogen-activated protein kinaseType III pathwayWild-type Y. pseudotuberculosisWild-type strainTNF-alphaPathogenic Yersinia sppYop genesYop proteinsYop secretionProtein kinaseMAP kinaseTranslational levelMutantsExposure of macrophagesYopJYersinia pseudotuberculosisSustained activationMacrophage TNF-α productionJNKP38Yersinia sppTumor necrosis factor alphaJ774A.1 murine macrophages
1997
TNF initiates E-selectin transcription in human endothelial cells through parallel TRAF-NF-kappa B and TRAF-RAC/CDC42-JNK-c-Jun/ATF2 pathways.
Min W, Pober JS. TNF initiates E-selectin transcription in human endothelial cells through parallel TRAF-NF-kappa B and TRAF-RAC/CDC42-JNK-c-Jun/ATF2 pathways. The Journal Of Immunology 1997, 159: 3508-18. PMID: 9317150, DOI: 10.4049/jimmunol.159.7.3508.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 2Antigens, SurfaceCalcium-Calmodulin-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinEndothelium, VascularE-SelectinGTP-Binding ProteinsHumansJNK Mitogen-Activated Protein KinasesMitogen-Activated Protein KinasesNF-kappa BPhosphorylationPromoter Regions, GeneticProto-Oncogene Proteins c-junrac GTP-Binding ProteinsReceptors, Tumor Necrosis FactorTranscription FactorsTranscription, GeneticTumor Necrosis Factor Receptor-Associated Peptides and ProteinsTumor Necrosis Factor-alphaUmbilical VeinsConceptsTransient overexpressionHuman endothelial cellsC-JunSelectin transcriptionATF2/c-JunN-terminalATF2 pathwayPromoter-reporter geneKappa B elementCAMP-responsive elementEndothelial cellsDomain phosphorylationEndogenous JNKAdaptor proteinInactive JNKNF-kappa BGene transcriptionGene promoterKappa BJNK activationKinase 1TranscriptionTRAF2 proteinCdc42JNK
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