2015
Partial Liver Kinase B1 (LKB1) Deficiency Promotes Diastolic Dysfunction, De Novo Systolic Dysfunction, Apoptosis, and Mitochondrial Dysfunction With Dietary Metabolic Challenge
Miller EJ, Calamaras T, Elezaby A, Sverdlov A, Qin F, Luptak I, Wang K, Sun X, Vijay A, Croteau D, Bachschmid M, Cohen RA, Walsh K, Colucci WS. Partial Liver Kinase B1 (LKB1) Deficiency Promotes Diastolic Dysfunction, De Novo Systolic Dysfunction, Apoptosis, and Mitochondrial Dysfunction With Dietary Metabolic Challenge. Journal Of The American Heart Association 2015, 5: e002277. PMID: 26722122, PMCID: PMC4859355, DOI: 10.1161/jaha.115.002277.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsApoptosisApoptosis Regulatory ProteinsCaspase 3DiastoleDiet, High-FatDietary SucroseDisease Models, AnimalGenetic Predisposition to DiseaseHeterozygoteHypertrophy, Left VentricularMice, KnockoutMitochondria, HeartMyocardiumPhenotypeProtein Serine-Threonine KinasesSignal TransductionSystoleTime FactorsTumor Suppressor Protein p53Tumor Suppressor ProteinsVentricular Dysfunction, LeftVentricular Function, LeftVentricular RemodelingConceptsHigh-sucrose dietSystolic dysfunctionDiastolic dysfunctionLiver kinase B1Metabolic heart diseaseDietary excessHeart diseaseMyocardial hypertrophyDe novo appearanceControl dietRestrictive filling patternSevere diastolic dysfunctionLeft ventricular dilationMitochondrial dysfunctionMetabolic stressWild-type miceHigh-sucrose feedingNovo appearanceP53/PUMAMore hypertrophyDiastolic functionMyocardial dysfunctionVentricular hypertrophyVentricular dilationSevere mitochondrial dysfunction
2014
A novel LKB1 isoform enhances AMPK metabolic activity and displays oncogenic properties
Dahmani R, Just P, Delay A, Canal F, Finzi L, Prip-Buus C, Lambert M, Sujobert P, Buchet-Poyau K, Miller E, Cavard C, Marmier S, Terris B, Billaud M, Perret C. A novel LKB1 isoform enhances AMPK metabolic activity and displays oncogenic properties. Oncogene 2014, 34: 2337-2346. PMID: 24998845, DOI: 10.1038/onc.2014.182.Peer-Reviewed Original ResearchConceptsLKB1 tumor suppressor geneTumor suppressor genePolarizing activitySuppressor geneOncogenic propertiesN-terminal regionCell polarityMaster kinaseMetabolic activityAutoinhibitory domainAlternative transcriptionKinase domainNovel isoformMetabolic sensorSame locusInternal initiationLKB1LKB1 mRNANCI-H460 cellsEnergetic metabolismLung cancer cell linesCancer cell linesDirect interactionIsoformsCell lines
2008
Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart
Miller EJ, Li J, Leng L, McDonald C, Atsumi T, Bucala R, Young LH. Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature 2008, 451: 578-582. PMID: 18235500, DOI: 10.1038/nature06504.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntigens, Differentiation, B-LymphocyteCoronary Artery DiseaseEnzyme ActivationGenetic Predisposition to DiseaseGenotypeGlucoseHistocompatibility Antigens Class IIHumansHypoxiaMacrophage Migration-Inhibitory FactorsMiceMultienzyme ComplexesMyocardial IschemiaMyocardial Reperfusion InjuryMyocardiumPolymorphism, GeneticPromoter Regions, GeneticProtein Serine-Threonine KinasesRatsSignal TransductionConceptsIschemic heartMacrophage migration inhibitory factorLower MIF levelsCoronary artery diseaseIschemic heart diseaseMigration inhibitory factorPotential risk markerMIF levelsArtery diseaseRisk markersHeart diseaseIschemic stressCytokine MIFInhibitory factorGlucose uptakePotential drug targetsDiseaseHeartDrug targetsCellular stress responseAMPKMaster regulatorNew studiesPatientsAtherosclerosis
2006
Activation of AMPK α- and γ-isoform complexes in the intact ischemic rat heart
Li J, Coven DL, Miller EJ, Hu X, Young ME, Carling D, Sinusas AJ, Young LH. Activation of AMPK α- and γ-isoform complexes in the intact ischemic rat heart. AJP Heart And Circulatory Physiology 2006, 291: h1927-h1934. PMID: 16648175, DOI: 10.1152/ajpheart.00251.2006.Peer-Reviewed Original ResearchConceptsAMPK activityAMPK complexAlpha subunit activationDifferent subunit isoformsSerine-threonine kinaseCellular metabolic processesGamma subunit isoformsRegulatory betaAlpha-subunit contentHeterotrimeric complexProtein kinaseAMPK αMultiple isoformsKinase activitySubunit isoformsMetabolic processesAMPK phosphorylationAMPKIsoformsPhysiological regulationKinaseMutationsComplexesKey rolePathophysiological importance
2005
AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart
Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR, Young LH. AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart. Circulation Research 2005, 97: 872-879. PMID: 16179588, DOI: 10.1161/01.res.0000187458.77026.10.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsAnisomycinCell HypoxiaEnzyme ActivationGlucoseGlucose Transporter Type 4Intracellular Signaling Peptides and ProteinsMaleMAP Kinase Kinase 3MiceMice, Inbred C57BLMice, TransgenicMultienzyme ComplexesMyocardial IschemiaP38 Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesProtein TransportRatsRats, Sprague-DawleyRibonucleotidesConceptsMitogen-activated protein kinaseP38 mitogen-activated protein kinaseMAPK kinase 3P38 MAPK activationAlpha2 catalytic subunitProtein kinaseMAPK activationCatalytic subunitGlucose transportStress-signaling pathwaysAMPK activator 5Role of AMPKProtein kinase 1Direct molecular targetP38 MAPK inhibitorMouse heartsAMPK complexProtein TAB1Scaffold proteinGLUT4 translocationUpstream kinaseAMPK activationKinase 3Kinase 1MAPK inhibitorDual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart
Baron SJ, Li J, Russell RR, Neumann D, Miller EJ, Tuerk R, Wallimann T, Hurley RL, Witters LA, Young LH. Dual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart. Circulation Research 2005, 96: 337-345. PMID: 15653571, DOI: 10.1161/01.res.0000155723.53868.d2.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine MonophosphateAdenosine TriphosphateAminoimidazole CarboxamideAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsInfusions, IntravenousMaleMultienzyme ComplexesMyocardial IschemiaMyocardiumPhosphorylationProtein KinasesProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyRecombinant ProteinsRibonucleotidesConceptsRecombinant AMPKAMPKK activityAMPK phosphorylationPhosphorylation of Thr172Gamma regulatory subunitsIschemic heartImportant signaling proteinAlpha catalytic subunitRat heartHeterotrimeric AMPKAMPKKHeterotrimeric complexActivation loopRegulatory subunitKinase actionSignaling proteinsCatalytic subunitProtein kinaseAMPK activityLow-flow ischemiaGamma subunitsAMPKInteraction of AMPPhosphorylationAddition of AMP