2022
SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies
Leveille E, Chan LN, Mirza AS, Kume K, Müschen M. SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies. Cellular Signalling 2022, 94: 110331. PMID: 35398488, DOI: 10.1016/j.cellsig.2022.110331.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutoimmune DiseasesAutoimmunityHumansLeukemia, Lymphocytic, Chronic, B-CellPhosphatidylinositol 3-KinasesReceptors, Antigen, B-CellSyk KinaseZAP-70 Protein-Tyrosine KinaseConceptsChronic lymphocytic leukemiaB-cell malignanciesT cell receptorB cell receptorB-cell chronic lymphocytic leukemiaPathological B-cellsPoor clinical outcomeAcute lymphoblastic leukemiaExpression of SykT lymphocyte developmentClinical outcomesAggressive diseaseActivation of NFATAutoimmune diseasesLymphoblastic leukemiaT lymphocytesLymphocytic leukemiaCell lymphomaLymphoid malignanciesB cellsPI3K-pathwayOncogenic driversMalignancyNegative selectionPremalignant cells
2021
Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer
Sadras T, Martin M, Kume K, Robinson ME, Saravanakumar S, Lenz G, Chen Z, Song JY, Siddiqi T, Oksa L, Knapp AM, Cutler J, Cosgun KN, Klemm L, Ecker V, Winchester J, Ghergus D, Soulas-Sprauel P, Kiefer F, Heisterkamp N, Pandey A, Ngo V, Wang L, Jumaa H, Buchner M, Ruland J, Chan WC, Meffre E, Martin T, Müschen M. Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer. Molecular Cell 2021, 81: 2094-2111.e9. PMID: 33878293, PMCID: PMC8239336, DOI: 10.1016/j.molcel.2021.03.043.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19AutoimmunityB-LymphocytesCalciumCell DifferentiationCell Transformation, NeoplasticEnzyme ActivationHumansImmune ToleranceLymphoma, B-CellMiceModels, GeneticNeoplasm ProteinsNeoplasmsNFATC Transcription FactorsPhosphatidylinositol 3-KinasesProtein BindingReceptors, Antigen, B-CellSignal TransductionSyk KinaseZAP-70 Protein-Tyrosine Kinase
2020
IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells
Lee J, Robinson ME, Ma N, Artadji D, Ahmed MA, Xiao G, Sadras T, Deb G, Winchester J, Cosgun KN, Geng H, Chan LN, Kume K, Miettinen TP, Zhang Y, Nix MA, Klemm L, Chen CW, Chen J, Khairnar V, Wiita AP, Thomas-Tikhonenko A, Farzan M, Jung JU, Weinstock DM, Manalis SR, Diamond MS, Vaidehi N, Müschen M. IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells. Nature 2020, 588: 491-497. PMID: 33149299, PMCID: PMC8087162, DOI: 10.1038/s41586-020-2884-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19B-LymphocytesCell Transformation, NeoplasticFemaleGerminal CenterHumansIntegrinsMembrane MicrodomainsMembrane ProteinsMiceMice, Inbred C57BLMice, Inbred NODModels, MolecularPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphorylationReceptors, Antigen, B-CellRNA-Binding ProteinsSignal TransductionConceptsPI3KCell leukemiaAntiviral effector functionsAntigen-specific antibodiesInterferon-induced transmembrane proteinsIFITM3 functionDevelopment of leukemiaCell surfacePoor outcomeOncogenic PI3KClinical cohortEffector functionsGerminal centersMouse modelB cellsExpression of IFITM3Malignant transformationAccumulation of PIP3PI3K signalsCell receptorNormal numbersLeukemiaDefective expressionEndosomal proteinIFITM3
2017
Inhibition of PI3K suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil
Ishida K, Ito C, Ohmori Y, Kume K, Sato KA, Koizumi Y, Konta A, Iwaya T, Nukatsuka M, Kobunai T, Takechi T, Nishizuka SS. Inhibition of PI3K suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil. Scientific Reports 2017, 7: 2262. PMID: 28536445, PMCID: PMC5442158, DOI: 10.1038/s41598-017-02548-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimetabolites, AntineoplasticCell Line, TumorCell ProliferationClass I Phosphatidylinositol 3-KinasesCodonDisease Models, AnimalDose-Response Relationship, DrugDrug Resistance, NeoplasmFluorouracilGenetic VariationHeterograftsHumansMiceNeoplasmsPhenotypePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProteomeProteomicsRibosomal Protein S6 Kinases, 90-kDaSignal TransductionConceptsOrthotopic xenograftsCancer cell subpopulationsCell subpopulationsGastric cancer cell line MKN45Gastric cancer chemotherapyRibosomal S6 kinase phosphorylationPI3K inhibitorsDisease relapseSequential administrationS6 kinase phosphorylationNude miceTumor propagationCancer chemotherapyK inhibitorsXenograftsPI3KChemotherapyRelapseTolerant subpopulationSubpopulationsKinase phosphorylationAdministrationCellsPhosphorylated phosphatidylinositidesMice