2025
Integrin-mediated mTOR signaling drives TGF-β overactivity and myxomatous mitral valve degeneration in hypomorphic fibrillin-1 mice
Gao F, Chen Q, Mori M, Li S, Ferrari G, Krane M, Fan R, Tellides G, Liu Y, Geirsson A. Integrin-mediated mTOR signaling drives TGF-β overactivity and myxomatous mitral valve degeneration in hypomorphic fibrillin-1 mice. Journal Of Clinical Investigation 2025 PMID: 40392604, DOI: 10.1172/jci183558.Peer-Reviewed Original ResearchMitral valve prolapseMyxomatous mitral valve degenerationValve prolapseMitral valve degenerationValve degenerationWeeks of ageTGF-bMgR miceMitral regurgitationAssociation of mitral valve prolapseProgression of mitral valve prolapseMTOR signalingMTOR inhibitionMitral valve diseaseMTOR activityTGF-b signalingLong-term inhibitionIncreased mTOR signalingMarfan syndromeMedical therapyLeukocyte infiltrationFBN1 variantsMacrophage recruitmentValve diseaseProlapse
2023
In Utero Electroporated Neurons for Medium-Throughput Screening of Compounds Regulating Neuron Morphology
Sokolov A, Aurich M, Bordey A. In Utero Electroporated Neurons for Medium-Throughput Screening of Compounds Regulating Neuron Morphology. ENeuro 2023, 10: eneuro.0160-23.2023. PMID: 37620147, PMCID: PMC10464655, DOI: 10.1523/eneuro.0160-23.2023.Peer-Reviewed Original ResearchConceptsSomatosensory cortexCortical pyramidal neuronsTreatment of epilepsyNeurite overgrowthNeurologic disabilityPyramidal neuronsSoma sizeNovel agentsCircuit alterationsSide effectsMorphologic assessmentMouse neuronsRelated disordersDiseased neuronsMTOR activatorDrug efficacyCandidate therapeuticsNeuronsNeuron morphologyMTOR activityMedium-throughput screeningNeurodevelopmental disordersNeurite lengthMorphologic measurementsDisorders
2018
mTOR Complex 1 Signaling Regulates the Generation and Function of Central and Effector Foxp3+ Regulatory T Cells
Sun I, Oh M, Zhao L, Patel C, Arwood M, Xu W, Tam A, Blosser R, Wen J, Powell J. mTOR Complex 1 Signaling Regulates the Generation and Function of Central and Effector Foxp3+ Regulatory T Cells. The Journal Of Immunology 2018, 201: 481-492. PMID: 29884702, PMCID: PMC6089237, DOI: 10.4049/jimmunol.1701477.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationFemaleForkhead Transcription FactorsImmunologic MemoryInducible T-Cell Co-Stimulator ProteinLymphocyte ActivationMaleMechanistic Target of Rapamycin Complex 1MiceProgrammed Cell Death 1 ReceptorRegulatory-Associated Protein of mTORSignal TransductionT-Lymphocytes, RegulatoryConceptsT cell activationT cellsCentral TregsGenetic deletionCell activationRegulatory T cell differentiationGeneration of TregsRegulatory T cellsEffector T cellsMemory-like phenotypeT cell differentiationInhibition of mTORSpare respiratory capacityEffector TregsRole of mTORPD-1Treg functionImmune microenvironmentMemory TregsTregsPharmacologic inhibitionDecreased expressionMammalian targetPharmacologic inhibitorsMTOR activity
2017
Inhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/mTOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells
Kim K, Park K, Kim S, Yu S, Park S, Kim Y, Seo Y, Ma J, Ahn S. Inhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/mTOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells. International Journal Of Molecular Sciences 2017, 18: 1088. PMID: 28524116, PMCID: PMC5454997, DOI: 10.3390/ijms18051088.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisAutophagyCell ProliferationExtracellular Signal-Regulated MAP KinasesFlavonoidsHumansImidazolesMaleMAP Kinase Signaling SystemMembrane Potential, Mitochondrialp38 Mitogen-Activated Protein KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktPyransPyridinesReactive Oxygen SpeciesTOR Serine-Threonine KinasesConceptsExtracellular signal-regulated kinasePI3K/Akt/mTORProstate cancer cellsAkt/mTORCancer cellsP38 MAPK-dependent signalingUpregulation of ERKSignal-regulated kinaseMAPK-dependent signalingP38 MAPK signaling pathwaysMitochondrial membrane potentialMAPK signaling pathwaysChemo-resistant cancersHuman prostate cancer cellsReactive oxygen species productionInhibition of autophagyPI3K inhibitorsPotential antitumor mechanismAcridine orange stainingCaspase-3 activityOxygen species productionSignaling pathwaysP38 inhibitorPropidium iodide assayMTOR activity
2016
mTOR has distinct functions in generating versus sustaining humoral immunity
Jones DD, Gaudette BT, Wilmore JR, Chernova I, Bortnick A, Weiss BM, Allman D. mTOR has distinct functions in generating versus sustaining humoral immunity. Journal Of Clinical Investigation 2016, 126: 4250-4261. PMID: 27760048, PMCID: PMC5096901, DOI: 10.1172/jci86504.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntibody FormationCell DifferentiationEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsImmunity, HumoralMechanistic Target of Rapamycin Complex 1MiceMice, TransgenicMultiprotein ComplexesPlasma CellsRegulatory-Associated Protein of mTORSignal TransductionTOR Serine-Threonine KinasesConceptsPlasma cellsBone marrow plasma cellsAntibody-associated diseaseSystemic lupus erythematosusMarrow plasma cellsAntibody-secreting plasma cellsPlasma cell differentiationLineage-specific deletionRole of mTORLupus erythematosusAcute treatmentExogenous antigensHumoral immunityAntibody responseSerum antibodiesMurine modelAntibody synthesisGerminal centersBone marrowCell differentiationMTOR inhibitionRobust protein synthesisMTOR activityRapamycin treatmentMTOR complex 1Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement
Hsieh LS, Wen JH, Claycomb K, Huang Y, Harrsch FA, Naegele JR, Hyder F, Buchanan GF, Bordey A. Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement. Nature Communications 2016, 7: 11753. PMID: 27249187, PMCID: PMC4895394, DOI: 10.1038/ncomms11753.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCognitive DysfunctionDisease Models, AnimalFemaleGene Expression RegulationGenes, ReporterGreen Fluorescent ProteinsHumansMaleMalformations of Cortical DevelopmentMiceNeuronsPrefrontal CortexSeizuresSignal TransductionSirolimusTOR Serine-Threonine KinasesWhite MatterConceptsFocal cortical dysplasiaCortical dysplasiaType II focal cortical dysplasiaWhite matter heterotopiasLayer 2/3 neuronsLife-long treatmentTonic-clonic seizuresNormal survival rateMedial prefrontal cortexLocal malformationsConvulsive seizuresPharmacoresistant epilepsySeizure activitySeizure generationSeizure occurrenceCommon causeCortical developmentMurine modelNeurocognitive impairmentSurvival rateSeizuresRapamycin withdrawalPrefrontal cortexMTOR activityRapamycin treatmentWAC Regulates mTOR Activity by Acting as an Adaptor for the TTT and Pontin/Reptin Complexes
David-Morrison G, Xu Z, Rui Y, Charng W, Jaiswal M, Yamamoto S, Xiong B, Zhang K, Sandoval H, Duraine L, Zuo Z, Zhang S, Bellen H. WAC Regulates mTOR Activity by Acting as an Adaptor for the TTT and Pontin/Reptin Complexes. Developmental Cell 2016, 36: 139-151. PMID: 26812014, PMCID: PMC4730548, DOI: 10.1016/j.devcel.2015.12.019.Peer-Reviewed Original ResearchConceptsPontin/Reptin complexMTOR activityRapamycin complex 1Energy statusRegulation of metabolismEnergy-dependent activationDrosophila screenEnergy-dependent mannerTTT complexRAG interactionsMTORC1 activityMechanistic targetReptinPhysical interactionRegulatorDimerizationNeuronal dysfunctionComplexesPontinHomologActivationComplexes 1AdaptorAutophagyMTOR
2015
Deletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation*
Cattin ME, Wang J, Weldrick JJ, Roeske CL, Mak E, Thorn SL, DaSilva JN, Wang Y, Lusis AJ, Burgon PG. Deletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation*. Journal Of Biological Chemistry 2015, 290: 26699-26714. PMID: 26359501, PMCID: PMC4646324, DOI: 10.1074/jbc.m115.678433.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsCardiomegalyCarrier ProteinsCo-Repressor ProteinsFemaleGene Expression RegulationGenome-Wide Association StudyHeart Function TestsHemodynamicsIsoproterenolMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumMyocytes, CardiacNuclear ProteinsPhosphorylationProto-Oncogene Proteins c-aktSignal TransductionStress, PhysiologicalTOR Serine-Threonine KinasesUltrasonographyConceptsAKT/mTOR pathwayGenome-wide association studiesAkt/mammalian targetMTOR pathwayAkt/mTOR activityAkt/mTORUnique proteinsUnknown functionAssociation studiesMTOR activityMammalian targetCardiac adaptationRegenerative abilityGenetic associationAdult heartPathwayHomeostasisMyocardial metabolic abnormalitiesNormal cardiac functionAdaptationEarly responseMetabolic abnormalitiesCardiac functionMLIPCardiac stress
2014
MEK-ERK1/2-Dependent FLNA Overexpression Promotes Abnormal Dendritic Patterning in Tuberous Sclerosis Independent of mTOR
Zhang L, Bartley CM, Gong X, Hsieh LS, Lin TV, Feliciano DM, Bordey A. MEK-ERK1/2-Dependent FLNA Overexpression Promotes Abnormal Dendritic Patterning in Tuberous Sclerosis Independent of mTOR. Neuron 2014, 84: 78-91. PMID: 25277454, PMCID: PMC4185153, DOI: 10.1016/j.neuron.2014.09.009.Peer-Reviewed Original ResearchConceptsDendritic complexityFLNA overexpressionDendritic abnormalitiesFLNA expressionDendritic patterningComplex dendritic arborsWild-type neuronsFilamin ADendritic arborsERK1/2-dependent mannerDendritic defectsNeurological defectsMEK-ERK1/2NeuronsMTOR activityNeurodevelopmental disordersNeurodevelopmental diseasesProtein filamin AAbnormalitiesMTOROverexpressionThe ATP-Competitive mTOR Inhibitor INK128 Enhances In Vitro and In Vivo Radiosensitivity of Pancreatic Carcinoma Cells
Hayman T, Wahba A, Rath B, Bae H, Kramp T, Shankavaram U, Camphausen K, Tofilon P. The ATP-Competitive mTOR Inhibitor INK128 Enhances In Vitro and In Vivo Radiosensitivity of Pancreatic Carcinoma Cells. Clinical Cancer Research 2014, 20: 110-119. PMID: 24198241, PMCID: PMC3947297, DOI: 10.1158/1078-0432.ccr-13-2136.Peer-Reviewed Original ResearchConceptsCap-complex formationGene translationPancreatic carcinoma cellsMTOR activityPancreatic carcinoma cell linesCell linesDNA double-strand breaksATP-competitive mTOR inhibitorsCarcinoma cellsΓH2AX fociCarcinoma cell linesPolysome-bound mRNADouble-strand breaksRadiation-induced γH2AX fociAberrant mTOR activityComplex formationDNA repairFibroblast cell lineMicroarray analysisRegulatory roleINK128Normal fibroblast cell lineMTOR inhibitionVivo radiosensitivityClonogenic survival
2013
Rheb Activation in Subventricular Zone Progenitors Leads to Heterotopia, Ectopic Neuronal Differentiation, and Rapamycin-Sensitive Olfactory Micronodules and Dendrite Hypertrophy of Newborn Neurons
Lafourcade CA, Lin TV, Feliciano DM, Zhang L, Hsieh LS, Bordey A. Rheb Activation in Subventricular Zone Progenitors Leads to Heterotopia, Ectopic Neuronal Differentiation, and Rapamycin-Sensitive Olfactory Micronodules and Dendrite Hypertrophy of Newborn Neurons. Journal Of Neuroscience 2013, 33: 2419-2431. PMID: 23392671, PMCID: PMC3711634, DOI: 10.1523/jneurosci.1840-12.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornCell DifferentiationCell EnlargementCell Line, TumorCell MovementCerebral VentriclesDendritesElectroporationFemaleHypertrophyMaleMiceMonomeric GTP-Binding ProteinsNeural Stem CellsNeurogenesisNeuronsNeuropeptidesOlfactory BulbRas Homolog Enriched in Brain ProteinSirolimusStem CellsTOR Serine-Threonine KinasesConceptsNeural progenitor cellsWild-type miceOlfactory bulbMTOR activitySynaptic inputsEctopic neuronal differentiationSubventricular zone neural progenitor cellsActive ras homologNeuronal differentiationGABAergic synaptic inputsTsc1 mutant miceSubventricular zone progenitorsDendritic complexityNewborn neuronsTuberous sclerosisOlig2 cellsHyperactive mTORHeterozygote miceCircuit formationAction potentialsNeuronal morphologyNewborn cellsMutant miceEctopic cellsMammalian target
2010
Expansion of CD3+/CD4+/CD25+/Foxp3+ T cells in rapamycin-treated lupus patients (143.52)
Perl A, Lai Z, Telarico T, Bartos A, Miklossy G, Hanczko R, Francis L, Tily H, Ramos I, Garcia R, Phillips P, Jimah J, Doherty E. Expansion of CD3+/CD4+/CD25+/Foxp3+ T cells in rapamycin-treated lupus patients (143.52). The Journal Of Immunology 2010, 184: 143.52-143.52. DOI: 10.4049/jimmunol.184.supp.143.52.Peer-Reviewed Original ResearchSLE patientsT cellsLupus patientsSystemic lupus erythematosus patientsMitochondrial hyperpolarizationFemale SLE patientsFrequency of TregsPrevalence of Foxp3Lupus erythematosus patientsT cell activationSLEDAI scoreHealthy controlsVivo treatmentPatientsB cellsFemale controlsTherapeutic efficacyCell activationMammalian targetVivo expansionMTOR activityRapamycin treatmentPotential mechanismsTregsRapamycin
2006
Suppression of Insulin Receptor Substrate 1 (IRS-1) Promotes Mammary Tumor Metastasis
Ma Z, Gibson S, Byrne M, Zhang J, White M, Shaw L. Suppression of Insulin Receptor Substrate 1 (IRS-1) Promotes Mammary Tumor Metastasis. Molecular And Cellular Biology 2006, 26: 9338-9351. PMID: 17030605, PMCID: PMC1698550, DOI: 10.1128/mcb.01032-06.Peer-Reviewed Original ResearchConceptsIRS-1Insulin receptor substrate (IRS) proteinsInsulin receptor substrate-1Wild-type levelsMetastasis suppressor functionReceptor substrate-1Cell surface receptorsBreast cancerSubstrate proteinsCytoplasmic adaptorAkt/mTOR activityMammary tumor metastasisSignificant homologySerine phosphorylationDistinct functionsSubstrate-1Mammary tumorsIRS-2MTOR activitySuppressor functionMetastatic mammary tumorsTumor cellsIR-1Surface receptorsBreast cancer metastasisEssential role of tuberous sclerosis genes TSC1 and TSC2 in NF-κB activation and cell survival
Ghosh S, Tergaonkar V, Rothlin CV, Correa RG, Bottero V, Bist P, Verma IM, Hunter T. Essential role of tuberous sclerosis genes TSC1 and TSC2 in NF-κB activation and cell survival. Cancer Cell 2006, 10: 215-226. PMID: 16959613, DOI: 10.1016/j.ccr.2006.08.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell SurvivalDNA DamageFibroblastsMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Monomeric GTP-Binding ProteinsNeuropeptidesNF-kappa BProto-Oncogene Proteins c-aktRas Homolog Enriched in Brain ProteinRNA, Small InterferingTranscription, GeneticTuberous Sclerosis Complex 1 ProteinTuberous Sclerosis Complex 2 ProteinTumor Necrosis Factor-alphaTumor Suppressor ProteinsConceptsNF-kappaB activationNF-kappaB transcriptional activationNF-κB activationNF-kappaB functionNF-kappaB signalingCell survivalPI-3K pathwayImportant survival factorActivity-dependent mannerTuberous sclerosis gene TSC1MTOR pathwayERK1/2 MAP kinasesReduced survivalSurvival factorK pathwayMTOR activityTSC2 expressionSurvivalCell survival responseGenes TSC1TNFalpha stimulationActivationInhibitionMAP kinaseInduction pathway
2004
Mammalian 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
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