Featured Publications
Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function
Schiapparelli P, Pirman NL, Mohler K, Miranda-Herrera PA, Zarco N, Kilic O, Miller C, Shah SR, Rogulina S, Hungerford W, Abriola L, Hoyer D, Turk BE, Guerrero-Cázares H, Isaacs FJ, Quiñones-Hinojosa A, Levchenko A, Rinehart J. Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function. Cell Reports 2021, 36: 109416. PMID: 34289367, PMCID: PMC8379681, DOI: 10.1016/j.celrep.2021.109416.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell Line, TumorCell MovementCell ProliferationEscherichia coliFemaleGlioblastomaHEK293 CellsHumansMaleMice, NudeMiddle AgedPhosphorylationPhosphoserineProtein Serine-Threonine KinasesRecombinant ProteinsSignal TransductionSmall Molecule LibrariesSubstrate SpecificityWNK Lysine-Deficient Protein Kinase 1ConceptsKinase networkAuthentic post-translational modificationsGenetic code expansionPost-translational modificationsProduction of proteinsSmall molecule kinase inhibitorsKinase inhibitorsGenetic codePhosphorylated proteinsCode expansionKinase proteinWNK kinasesPhysiological functionsWNK4 kinaseBiochemical propertiesGlioblastoma cellsKinaseBacterial strainsProteinDistinct sitesPhosphoserineSPAKBacteriaCellular systemsCellsTargeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes
Apostolidi M, Vathiotis IA, Muthusamy V, Gaule P, Gassaway BM, Rimm DL, Rinehart J. Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes. Cancer Research 2021, 81: 4346-4359. PMID: 34185676, PMCID: PMC8373815, DOI: 10.1158/0008-5472.can-20-4190.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsBiomarkers, TumorCarrier ProteinsCell Line, TumorCollagenCyclic N-OxidesDrug CombinationsGenome, HumanHumansIndolizinesLamininMCF-7 CellsMembrane ProteinsMiceNeoplasm InvasivenessNeoplasm TransplantationNeoplasmsOxidation-ReductionPhenotypePhosphorylationProtein IsoformsProteoglycansProteomicsPyridazinesPyridinium CompoundsPyrrolesPyruvate KinaseThyroid HormonesTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPyruvate kinase M2TEPP-46Breast cancerAggressive breast cancer cell phenotypesCharacteristic nuclear staining patternAggressive breast cancer subtypeAggressive breast cancer phenotypeBreast cancer cell phenotypeCDK inhibitor dinaciclibCombination of dinaciclibLack of biomarkersEffective therapeutic approachBreast cancer phenotypeBreast cancer subtypesCancer phenotypePhosphorylation of PKM2Cyclin-dependent kinase (CDK) pathwayMouse xenograft modelAggressive cancer phenotypeNuclear staining patternLower survival rateImpaired redox balancePrognostic valueCancer cell phenotype
2019
Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production
Gassaway BM, Cardone RL, Padyana AK, Petersen MC, Judd ET, Hayes S, Tong S, Barber KW, Apostolidi M, Abulizi A, Sheetz JB, Kshitiz, Aerni HR, Gross S, Kung C, Samuel VT, Shulman GI, Kibbey RG, Rinehart J. Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production. Cell Reports 2019, 29: 3394-3404.e9. PMID: 31825824, PMCID: PMC6951436, DOI: 10.1016/j.celrep.2019.11.009.Peer-Reviewed Original ResearchConceptsCyclin-dependent kinasesMetabolic control pointPhosphorylation sitesNuclear retentionCDK activityPKL activityDays high-fat dietKinase phosphorylationImportant enzymePyruvate kinaseHigh-fat dietS113KinaseEnzyme kineticsPhosphorylationAdditional control pointsRegulationGlucose productionHepatic glucose productionInsulin resistanceGlycolysisEnzymePKAPathwayActivity