2010
Leukemogenic Tyrosine Kinases Inhibit PKM2 to Promote the Warburg Effect and Tumor Growth
Hitosugi T, Kang S, Vander Heiden M, Chung T, Elf S, Lythgoe K, Dong S, Lonial S, Wang X, Chen G, Xie J, Gu T, Polakiewicz R, Roesel J, Boggon T, Khuri F, Gilliland D, Cantley L, Kaufman J, Chen J. Leukemogenic Tyrosine Kinases Inhibit PKM2 to Promote the Warburg Effect and Tumor Growth. Blood 2010, 116: 3142. DOI: 10.1182/blood.v116.21.3142.3142.Peer-Reviewed Original ResearchCancer cell metabolismTumor growthTyrosine kinaseWarburg effectCancer cellsMolecular mechanismsOxidative phosphorylationReduced lactate productionCell metabolismLeukemia cellsPyruvate kinase M2 isoformLeukemogenic tyrosine kinasesPhosphorylation of PKM2RNAi-mediated knockdownXenograft nude micePhospho-proteomics studiesInhibition of PKM2Leukemia/lymphoma syndromeHypoxia-inducible factor-1Oncogenic tyrosine kinasesTyrosine kinase pathwayGrowth factor receptorInducible factor-1Phosphotyrosine bindingDisease progression
2008
Disruption of the EGFR E884–R958 ion pair conserved in the human kinome differentially alters signaling and inhibitor sensitivity
Tang Z, Jiang S, Du R, Petri E, El-Telbany A, Chan P, Kijima T, Dietrich S, Matsui K, Kobayashi M, Sasada S, Okamoto N, Suzuki H, Kawahara K, Iwasaki T, Nakagawa K, Kawase I, Christensen J, Hirashima T, Halmos B, Salgia R, Boggon T, Kern J, Ma P. Disruption of the EGFR E884–R958 ion pair conserved in the human kinome differentially alters signaling and inhibitor sensitivity. Oncogene 2008, 28: 518-533. PMID: 19015641, PMCID: PMC2633425, DOI: 10.1038/onc.2008.411.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAMP-Activated Protein Kinase KinasesAnimalsChlorocebus aethiopsCOS CellsErbB ReceptorsErlotinib HydrochlorideFocal Adhesion Kinase 1HumansIndolesLung NeoplasmsMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mutation, MissensePiperazinesProtein ConformationProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-kitProto-Oncogene Proteins c-metProto-Oncogene Proteins c-retQuinazolinesReceptors, Growth FactorSulfonamidesConceptsHuman kinomeEpidermal growth factor receptorKinase substrate recognitionInhibitor sensitivityCancer-associated mutationsSystematic bioinformatics analysisTumor suppressor geneSmall molecule inhibitorsSubstrate recognitionProtein kinaseGrowth factor receptorBioinformatics analysisHomologous residuesDownstream signalingSequence analysisLysine residuesKinomeC-lobeConformational changesFamily inhibitorsMutation cataloguesAdjacent residuesMET inhibitor SU11274Factor receptorMutations
2005
Jak3 Kinase Domain Crystal Structures and Implications for Jak-Specific Drug Design.
Boggon T. Jak3 Kinase Domain Crystal Structures and Implications for Jak-Specific Drug Design. Blood 2005, 106: 69. DOI: 10.1182/blood.v106.11.69.69.Peer-Reviewed Original ResearchJAK3 kinase domainKinase domainDomain crystal structureResolution co-crystal structureJAK kinase family membersTyrosine kinaseLatent transcription factorsNon-receptor tyrosine kinaseActivation of transcriptionReceptor cytoplasmic tailKinase family membersRapid tyrosine phosphorylationThree-dimensional structural dataJAK-specific inhibitorDrug designTyrosine kinase activityFurther crystal structuresAutoinhibited conformationCo-crystal structureJAK activityConformational plasticityCytoplasmic tailTranscription factorsTranscription (STAT) proteinsGrowth factor receptor