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
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