2023
ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells
Bergaggio E, Tai W, Aroldi A, Mecca C, Landoni E, Nüesch M, Mota I, Metovic J, Molinaro L, Ma L, Alvarado D, Ambrogio C, Voena C, Blasco R, Li T, Klein D, Irvine D, Papotti M, Savoldo B, Dotti G, Chiarle R. ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells. Cancer Cell 2023, 41: 2100-2116.e10. PMID: 38039964, PMCID: PMC10793157, DOI: 10.1016/j.ccell.2023.11.004.Peer-Reviewed Original ResearchConceptsALK inhibitorsALK expressionChimeric antigen receptor TBest tumor antigensPromising clinical activityExpression of ALKMost normal tissuesHematologic malignanciesClinical activityMost neuroblastomasAnaplastic lymphoma kinase (ALK) receptorTherapeutic successTumor antigensPotent efficacySolid tumorsTherapeutic efficacyNeuroblastomaTumor growthOncogenic driversNeuroblastoma cellsNormal tissuesALKKinase receptorsMonotherapyInhibitors
2022
317 ALK chimeric antigen receptor T cells cooperate with ALK inhibitors to target neuroblastoma cells with low target density
Bergaggio E, Tai W, Aroldi A, Landoni E, Nuesch M, Mota I, Metovic J, Ma L, Alvarado D, Ambrogio C, Voena C, Blasco R, Li T, Klein D, Irvine D, Papotti M, Savoldo B, Dotti G, Chiarle R. 317 ALK chimeric antigen receptor T cells cooperate with ALK inhibitors to target neuroblastoma cells with low target density. 2022, a333-a333. DOI: 10.1136/jitc-2022-sitc2022.0317.Peer-Reviewed Original Research
2016
Discovery of the First Pathogenic Human EPO Mutation Provides Mechanistic Insight into Cytokine Signaling
Kim A, Ulirsch J, Wilmes S, Unal E, Moraga I, Karakukcu M, Yuan D, Kazerounian S, Gupta N, Gabriel S, Lander E, Patiroglu T, Ozcan A, Ozdemir M, Garcia C, Piehler J, Gazda H, Klein D, Sankaran V. Discovery of the First Pathogenic Human EPO Mutation Provides Mechanistic Insight into Cytokine Signaling. Blood 2016, 128: 331. DOI: 10.1182/blood.v128.22.331.331.Peer-Reviewed Original ResearchDiamond-Blackfan anemiaWhole-exome sequencing dataEPO receptorPotent concentrationAllogeneic bone marrow transplantBone marrow transplantBone marrow failure disordersYears of ageIntracellular flow cytometryMarrow failure disordersSerum EPO levelsExome sequencing dataMajority of casesAnemia correctionHost diseaseSevere graftDonor chimerismRed blood cellsMarrow transplantResultant complicationsLow doseRare caseSide effectsPatientsBone marrow
2009
Structural basis for EGFR ligand sequestration by Argos
Klein D, Stayrook S, Shi F, Narayan K, Lemmon M. Structural basis for EGFR ligand sequestration by Argos. The FASEB Journal 2009, 23: 883.7-883.7. DOI: 10.1096/fasebj.23.1_supplement.883.7.Peer-Reviewed Original ResearchEpidermal growth factor receptorHuman urokinase-type plasminogen activator receptorDiverse developmental processesClamp-like structureEGF-like domainGrowth factor ligandsArgos functionMammalian counterpartsLigand sequestrationEGF-like modulesUrokinase-type plasminogen activator receptorEGF domainsEGF ligandGrowth factor receptorEssential regulatorStructural basisDevelopmental processesStructural homologuesEGFR ligandsFactor ligandHuman cancersPlasminogen activator receptorFactor receptorErbB/Inappropriate activationErbB2/HER2/Neu resembles an autoinhibited invertebrate EGF receptor
Alvarado D, Klein D, Lemmon M. ErbB2/HER2/Neu resembles an autoinhibited invertebrate EGF receptor. The FASEB Journal 2009, 23: 884.3-884.3. DOI: 10.1096/fasebj.23.1_supplement.884.3.Peer-Reviewed Original ResearchReceptor tyrosine kinase ErbB2Human cancersAutoinhibitory interactionsExtracellular regionInterdomain interactionsEGF receptorErbB2 signalingOrphan receptorOncogenic propertiesHuman EGFRErbB receptorsImportant therapeutic targetErbB2Structural studiesTherapeutic targetNovel aspectsReceptorsAutoinhibitoryAutoinhibitionSignalingOverexpressionImportant implicationsRegulationTherapeutic approachesEGFR
2001
High-Affinity Binding of a FYVE Domain to Phosphatidylinositol 3-Phosphate Requires Intact Phospholipid but Not FYVE Domain Oligomerization †
Sankaran V, Klein D, Sachdeva M, Lemmon M. High-Affinity Binding of a FYVE Domain to Phosphatidylinositol 3-Phosphate Requires Intact Phospholipid but Not FYVE Domain Oligomerization †. Biochemistry 2001, 40: 8581-8587. PMID: 11456498, DOI: 10.1021/bi010425d.Peer-Reviewed Original ResearchMeSH KeywordsBinding, CompetitiveBlood ProteinsCarrier ProteinsCation Transport ProteinsGlutathione TransferaseGuanine Nucleotide Exchange FactorsHeLa CellsHumansLiposomesMonosaccharide Transport ProteinsPhosphatidylinositol PhosphatesPhospholipidsPhosphoproteinsProtein BindingProtein Structure, TertiaryProteinsRecombinant Fusion ProteinsSymportersZinc FingersConceptsFYVE domainPH domainDomain oligomerizationSpecific PH domainsVacuolar protein sortingPleckstrin homology domainLipid headgroupsProtein sortingMembrane trafficHomology domainSpecific phosphoinositideLike domainEndosomal maturationHigh-affinity bindingPreferred lipidPhospholipase CPhosphoinositideIntact lipidsIntact phospholipidsOligomerizationDomainMembrane
1998
Specificity and Promiscuity in Phosphoinositide Binding by Pleckstrin Homology Domains*
Kavran J, Klein D, Lee A, Falasca M, Isakoff S, Skolnik E, Lemmon M. Specificity and Promiscuity in Phosphoinositide Binding by Pleckstrin Homology Domains*. Journal Of Biological Chemistry 1998, 273: 30497-30508. PMID: 9804818, DOI: 10.1074/jbc.273.46.30497.Peer-Reviewed Original ResearchConceptsPleckstrin homology domainPH domainGrp1 PH domainD-myo-inositolParticular phosphoinositidesPhosphoinositide bindingHomology domainDependent membrane recruitmentDifferent PH domainsPH domain bindsSmall protein modulesSoluble inositol phosphatesMembrane recruitmentDomain bindsProtein modulesSpecific phosphoinositideMammalian cellsPlasma membraneSingle speciesAbundant speciesMultiple phosphoinositidesCellular membranesPhosphoinositidePI 3Clear specificityThe Pleckstrin Homology Domains of Dynamin Isoforms Require Oligomerization for High Affinity Phosphoinositide Binding*
Klein D, Lee A, Frank D, Marks M, Lemmon M. The Pleckstrin Homology Domains of Dynamin Isoforms Require Oligomerization for High Affinity Phosphoinositide Binding*. Journal Of Biological Chemistry 1998, 273: 27725-27733. PMID: 9765310, DOI: 10.1074/jbc.273.42.27725.Peer-Reviewed Original Research