2023
STAT5-Feedback Controls Distinct Metabolic States for Dynamic Transitions between Cellular Activation and Quiescence in Acute Lymphoblastic Leukemia
Kume K, Chen Z, Robinson M, Chan L, Leveille E, Cosgun K, Cheng Z, Arce D, Khanduja D, Graeber T, Müschen M. STAT5-Feedback Controls Distinct Metabolic States for Dynamic Transitions between Cellular Activation and Quiescence in Acute Lymphoblastic Leukemia. Blood 2023, 142: 2977. DOI: 10.1182/blood-2023-191006.Peer-Reviewed Original ResearchB-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaLymphoblastic leukemiaPharmacological inhibitionGenetic deletionCellular activationReceptor signalingCell deathBone marrow relapsePoor overall outcomePoor clinical outcomeLeukemia-initiating capacityOncogenic STAT5Mass spectrometry-based metabolomics analysisExpression levelsPhosphorylation of STAT5Flow cytometry analysisMetabolic statePositive MRDRole of mTORMarrow relapseAggressive courseClinical outcomesExcessive protein synthesisMetabolic outcomes
2022
mTOR inhibition prevents angiotensin II–induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice
He C, Jiang B, Wang M, Ren P, Murtada SI, Caulk AW, Li G, Qin L, Assi R, Lovoulos CJ, Schwartz MA, Humphrey JD, Tellides G. mTOR inhibition prevents angiotensin II–induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice. JCI Insight 2022, 7: e155815. PMID: 35132962, PMCID: PMC8855820, DOI: 10.1172/jci.insight.155815.Peer-Reviewed Original ResearchConceptsApoE-deficient miceAngiotensin IIVascular wall cellsAortic tearAortic ruptureMTOR inhibitionSmooth muscle cell hypertrophyMatricellular proteinWall cellsSuprarenal abdominal aortaMuscle cell hypertrophyExtracellular matrix accumulationInhibition of mTORRole of mTORSubadventitial hematomaFree ruptureAortic dissectionAortic diseaseAortic aneurysmSignificant dissectionAbdominal aortaHemorrhagic lesionsExtensive dissectionMetalloproteinase expressionCell hypertrophy
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
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 1
2009
High Expression of Mammalian Target of Rapamycin Is Associated with Better Outcome for Patients with Early Stage Lung Adenocarcinoma
Anagnostou VK, Bepler G, Syrigos KN, Tanoue L, Gettinger S, Homer RJ, Boffa D, Detterbeck F, Rimm DL. High Expression of Mammalian Target of Rapamycin Is Associated with Better Outcome for Patients with Early Stage Lung Adenocarcinoma. Clinical Cancer Research 2009, 15: 4157-4164. PMID: 19509151, DOI: 10.1158/1078-0432.ccr-09-0099.Peer-Reviewed Original ResearchConceptsLung cancer patientsMTOR expressionCancer patientsMammalian targetEarly-stage lung adenocarcinomaHigh mTOR expressionIndependent lower riskMedian overall survivalStage IA patientsProtein expressionSubgroup of patientsLung adenocarcinoma patientsStage lung adenocarcinomaMTOR protein expressionRole of mTOROverall survivalPathologic characteristicsPatient survivalValidation cohortAdenocarcinoma groupAdenocarcinoma patientsPrognostic stratificationLung cancerTraining cohortFavorable outcome
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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