2013
mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK
Melemedjian OK, Khoutorsky A, Sorge RE, Yan J, Asiedu MN, Valdez A, Ghosh S, Dussor G, Mogil JS, Sonenberg N, Price TJ. mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK. Pain 2013, 154: 1080-1091. PMID: 23607966, PMCID: PMC3742001, DOI: 10.1016/j.pain.2013.03.021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDown-RegulationEnzyme ActivationFeedback, PhysiologicalInsulin Receptor Substrate ProteinsMaleMAP Kinase Signaling SystemMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, Inbred ICRMultiprotein ComplexesPainRatsRats, Sprague-DawleySensory Receptor CellsSirolimusTOR Serine-Threonine KinasesConceptsSpontaneous painMechanical hypersensitivitySensory neuronsDevelopment of painPotential treatment optionSensory neuron sensitizationRapamycin complex 1 (mTORC1) inhibitorsExtracellular signal-regulated kinase (ERK) pathwaySignal-regulated kinase pathwaySuppression of S6K1Chronic treatmentPain conditionsPain therapeuticsTransplant rejectionAdenosine monophosphate-activated protein kinase (AMPK) activatorProtein kinase activatorsTreatment optionsAntidiabetic drugsPainSensory hypersensitivityMTOR pathwayNegative feedback loopCertain cancersMammalian targetMTORC1 inhibition
2006
Essential 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