2023
Inhibition of Abelson Tyrosine-Protein Kinase 2 Suppresses the Development of Alcohol-Associated Liver Disease by Decreasing PPARgamma Expression
Malnassy G, Keating C, Gad S, Bridgeman B, Perera A, Hou W, Cotler S, Ding X, Choudhry M, Sun Z, Koleske A, Qiu W. Inhibition of Abelson Tyrosine-Protein Kinase 2 Suppresses the Development of Alcohol-Associated Liver Disease by Decreasing PPARgamma Expression. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 685-709. PMID: 37460041, PMCID: PMC10520367, DOI: 10.1016/j.jcmgh.2023.07.006.Peer-Reviewed Original ResearchConceptsAlcohol-fed miceLiver diseaseALD pathogenesisPPARγ expressionLiver injuryAlcohol feedingKnockout miceAlcohol-associated liver diseaseLiver tissueC57BL6/J miceAlcohol-induced accumulationAlcohol-induced steatosisOil Red O stainingWild-type miceHypoxia inducible factor 1 subunit alphaTreatment of ALDPPARγ protein expressionRed O stainingLiver-specific knockoutSubsequent lipid accumulationSubsequent RNA sequencingPotential molecular targetsAbl kinase inhibitorsQuantitative polymerase chain reactionLipid droplet formation
2019
Trio Haploinsufficiency Causes Neurodevelopmental Disease-Associated Deficits
Katrancha SM, Shaw JE, Zhao AY, Myers SA, Cocco AR, Jeng AT, Zhu M, Pittenger C, Greer CA, Carr SA, Xiao X, Koleske AJ. Trio Haploinsufficiency Causes Neurodevelopmental Disease-Associated Deficits. Cell Reports 2019, 26: 2805-2817.e9. PMID: 30840899, PMCID: PMC6436967, DOI: 10.1016/j.celrep.2019.02.022.Peer-Reviewed Original ResearchConceptsHeterozygous coding mutationsDendritic spine densityHippocampus of miceNeurodevelopmental disordersLong-term potentiationDendritic spine defectsPostsynaptic deficitsSpine densityCortical synapsesDendritic arborizationExcitatory neuronsMotor coordinationHaploinsufficient miceKnockout miceTherapeutic interventionsBipolar disorderProtein kinase A (PKA) signalingNeuronal structuresSpine defectsIncreases anxietyMiceDisordersDeficitsCoding mutationsA Signaling
2017
CNS Neurons Deposit Laminin α5 to Stabilize Synapses
Omar MH, Campbell M, Xiao X, Zhong Q, Brunken WJ, Miner JH, Greer CA, Koleske AJ. CNS Neurons Deposit Laminin α5 to Stabilize Synapses. Cell Reports 2017, 21: 1281-1292. PMID: 29091766, PMCID: PMC5776391, DOI: 10.1016/j.celrep.2017.10.028.Peer-Reviewed Original ResearchConceptsDendritic spine head sizeLaminin α5Larger postsynaptic densitiesDendritic spine densitySpine head sizeAge-dependent lossDendritic spine sizeEnhanced neurotransmissionSpine densityHippocampal neuronsDendritic spinesConditional deletionLaminin β2Postsynaptic densitySynapsesSpine sizeEarly adulthoodBehavioral defectsNeuronsBrainHead sizeMolecular mechanismsΑ5LamininNeurotransmissionNeurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity
Katrancha SM, Wu Y, Zhu M, Eipper BA, Koleske AJ, Mains RE. Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity. Human Molecular Genetics 2017, 26: 4728-4740. PMID: 28973398, PMCID: PMC5886096, DOI: 10.1093/hmg/ddx355.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsDatabases, Nucleic AcidGuanine Nucleotide Exchange FactorsGuanosine DiphosphateGuanosine TriphosphateHEK293 CellsHumansMiceMice, KnockoutMutationNeurodevelopmental DisordersProtein DomainsProtein Serine-Threonine KinasesRac1 GTP-Binding ProteinRho GTP-Binding ProteinsRhoA GTP-Binding ProteinConceptsDe novo mutationsNeurodevelopmental disordersRare sequence variantsTriple functional domain proteinNovo mutationsComplex neurodevelopmental disorderBipolar disorderTherapeutic progressSequence variantsImpaired inhibitionProtein levelsDisordersMolecular pathwaysMillions of peopleIntellectual disabilityRare variantsNeurite outgrowthGenetic damageFactor activityMutationsExchange factor activityDistinct specificitiesPoor understandingRac1ActivityThe Abl‐1 Kinase is Dispensable for NK Cell Inhibitory Signalling and is not Involved in Murine NK Cell Education
Ganesan S, Luu TT, Chambers BJ, Meinke S, Brodin P, Vivier E, Wetzel DM, Koleske AJ, Kadri N, Höglund P. The Abl‐1 Kinase is Dispensable for NK Cell Inhibitory Signalling and is not Involved in Murine NK Cell Education. Scandinavian Journal Of Immunology 2017, 86: 135-142. PMID: 28605050, PMCID: PMC5568956, DOI: 10.1111/sji.12574.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, LyCell DifferentiationCells, CulturedCytotoxicity, ImmunologicImmunity, InnateInterferon-gammaKiller Cells, NaturalLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutNatural Cytotoxicity Triggering Receptor 1NK Cell Lectin-Like Receptor Subfamily CProto-Oncogene Proteins c-ablSignal TransductionConceptsNK cell educationNK cellsCell educationNatural killer cell responsivenessYAC-1 tumor cellsNK cell inhibitionNK cell functionHuman NK cellsMurine NK cellsMHC class IC-AblC-Abl expressionInhibitory Ly49Normal inhibitoryNKG2A receptorsInhibitory receptorsCell responsivenessReceptor stimulationReceptor repertoireInhibitory signalingTumor cellsITAM receptorsClass ICell inhibitionCell function
2016
Reciprocal stabilization of ABL and TAZ regulates osteoblastogenesis through transcription factor RUNX2
Matsumoto Y, La Rose J, Kent OA, Wagner MJ, Narimatsu M, Levy AD, Omar MH, Tong J, Krieger JR, Riggs E, Storozhuk Y, Pasquale J, Ventura M, Yeganeh B, Post M, Moran MF, Grynpas MD, Wrana JL, Superti-Furga G, Koleske AJ, Pendergast AM, Rottapel R. Reciprocal stabilization of ABL and TAZ regulates osteoblastogenesis through transcription factor RUNX2. Journal Of Clinical Investigation 2016, 126: 4482-4496. PMID: 27797343, PMCID: PMC5127668, DOI: 10.1172/jci87802.Peer-Reviewed Original ResearchConceptsLineage-specifying transcription factorsReciprocal stabilizationAdaptor protein 3BP2TAZ nuclear localizationTranscription factor complexTyrosine kinase AblTranscription factor Runx2Transcriptional coactivator TAZLineage-specific maturationMetazoan organismsCellular identityOsteoblast expansionTranscriptional positive feedbackTranscription factorsSkeletal formationFactor complexNuclear localizationOwn expressionPositive feedback loopGenetic dataOsteoblast lineageMaturation programOsteoblast differentiationDevelopmental networksTAZDisruption of Coordinated Presynaptic and Postsynaptic Maturation Underlies the Defects in Hippocampal Synapse Stability and Plasticity in Abl2/Arg-Deficient Mice
Xiao X, Levy AD, Rosenberg BJ, Higley MJ, Koleske AJ. Disruption of Coordinated Presynaptic and Postsynaptic Maturation Underlies the Defects in Hippocampal Synapse Stability and Plasticity in Abl2/Arg-Deficient Mice. Journal Of Neuroscience 2016, 36: 6778-6791. PMID: 27335408, PMCID: PMC4916252, DOI: 10.1523/jneurosci.4092-15.2016.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornDendritic SpinesExcitatory Amino Acid AgentsFemaleGene Expression Regulation, DevelopmentalGlutamic AcidHippocampusHSP70 Heat-Shock ProteinsIn Vitro TechniquesMaleMiceMice, Inbred C57BLMice, KnockoutNeuronal PlasticityNeurotransmitter AgentsProtein-Tyrosine KinasesReceptors, GlutamateReceptors, N-Methyl-D-AspartateSubcellular FractionsSynapsesSynaptic PotentialsConceptsNMDA receptorsHippocampal synapsesEarly adulthoodFocal glutamate uncagingImmature glutamatergic synapsesDendritic spine numberNormal synaptic plasticityPostnatal day 21NMDA receptor currentsLate postnatal developmentHigh release probabilityArg kinaseForms of plasticityGlutamate uncagingSynapse lossPresynaptic sitesGlutamatergic synapsesSynapse stabilityPostsynaptic sitesSynaptic stabilityCultured neuronsMice ageReceptor currentsDay 21Synaptic plasticity
2014
Two Amino Acid Residues Confer Different Binding Affinities of Abelson Family Kinase Src Homology 2 Domains for Phosphorylated Cortactin*
Gifford SM, Liu W, Mader CC, Halo TL, Machida K, Boggon TJ, Koleske AJ. Two Amino Acid Residues Confer Different Binding Affinities of Abelson Family Kinase Src Homology 2 Domains for Phosphorylated Cortactin*. Journal Of Biological Chemistry 2014, 289: 19704-19713. PMID: 24891505, PMCID: PMC4094080, DOI: 10.1074/jbc.m114.556480.Peer-Reviewed Original ResearchConceptsAbl SH2 domainSH2 domainAbl family kinasesFamily kinasesSrc homology 2 domainCell edge protrusionAbl SH2Similar N-terminal sequencesImportant non-redundant rolesWild-type levelsAmino acid sequenceAmino acid positionsN-terminal sequenceNon-redundant roleCell morphogenesisArg substrateCellular functionsSpecific phosphotyrosineCell peripheryAcid sequenceSerine 187Edge protrusionTarget proteinsType levelsDifferent binding affinities
2012
The Abl and Arg Kinases Mediate Distinct Modes of Phagocytosis and Are Required for Maximal Leishmania Infection
Wetzel DM, McMahon-Pratt D, Koleske AJ. The Abl and Arg Kinases Mediate Distinct Modes of Phagocytosis and Are Required for Maximal Leishmania Infection. Molecular And Cellular Biology 2012, 32: 3176-3186. PMID: 22665498, PMCID: PMC3434515, DOI: 10.1128/mcb.00086-12.Peer-Reviewed Original ResearchConceptsComplement receptor 3Leishmania infectionIgG-coated beadsMurine cutaneous leishmaniasisPotential therapeutic targetLeishmania uptakeVisceral diseaseObligate intracellular parasitesCutaneous leishmaniasisTherapeutic targetFc receptorsAmastigote uptakeTreatment resultsReceptor 3Small lesionsInfection severityLeishmania amazonensisKinase inhibitorsIntracellular parasitesBead phagocytosisPhagocytosisReceptorsC3biInfectionLeishmaniasisIntegrin β1 Signals through Arg to Regulate Postnatal Dendritic Arborization, Synapse Density, and Behavior
Warren MS, Bradley WD, Gourley SL, Lin YC, Simpson MA, Reichardt LF, Greer CA, Taylor JR, Koleske AJ. Integrin β1 Signals through Arg to Regulate Postnatal Dendritic Arborization, Synapse Density, and Behavior. Journal Of Neuroscience 2012, 32: 2824-2834. PMID: 22357865, PMCID: PMC3313657, DOI: 10.1523/jneurosci.3942-11.2012.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-FetoproteinsAnalysis of VarianceAnimalsAnimals, NewbornAvoidance LearningBasic Helix-Loop-Helix Transcription FactorsCells, CulturedCocaineDendritesEnzyme-Linked Immunosorbent AssayExploratory BehaviorGreen Fluorescent ProteinsGTPase-Activating ProteinsHippocampusImmunoprecipitationIntegrin beta1MaleMiceMice, KnockoutMutationNerve Tissue ProteinsNeuronsOrgan Culture TechniquesPost-Synaptic DensityProtein BindingRecognition, PsychologyRepressor ProteinsSignal TransductionSrc Homology DomainsSynapsesConceptsIntegrin β1Vertebrate nervous systemExtracellular matrix receptorsGenetic experimentsIntracellular tailGenetic manipulationRhoA GTPaseArg kinaseMatrix receptorsProper hippocampal functionProper developmentSynapse maintenanceDose-sensitive mannerImpaired hippocampus-dependent learningHippocampal dendritic arborsHippocampal synapse lossDendritic arbor sizeHippocampus-dependent learningΒ1ArgSelective lossGTPaseP190RhoGAPPsychomotor sensitivityKinaseArg Kinase Regulates Prefrontal Dendritic Spine Refinement and Cocaine-Induced Plasticity
Gourley SL, Olevska A, Warren MS, Taylor JR, Koleske AJ. Arg Kinase Regulates Prefrontal Dendritic Spine Refinement and Cocaine-Induced Plasticity. Journal Of Neuroscience 2012, 32: 2314-2323. PMID: 22396406, PMCID: PMC3386297, DOI: 10.1523/jneurosci.2730-11.2012.Peer-Reviewed Original ResearchConceptsSpine densityAdolescent wild-type mouseHippocampal CA1 pyramidal neuronsDendritic spine densityCA1 pyramidal neuronsPostnatal day 60Wild-type miceDendritic spine developmentCocaine-Induced PlasticityAddictive-like behaviorsPyramidal neuronsCocaine sensitizationDendritic spinesPsychomotor sensitizationProtective consequencesSpine headsNeuropsychiatric disordersOrbitofrontal cortexDay 60Local applicationArg inhibitionPsychomotor sensitivityIntracellular mechanismsPsychostimulant sensitivitySpine development
2010
Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function
Ko HS, Lee Y, Shin JH, Karuppagounder SS, Gadad BS, Koleske AJ, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM. Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 16691-16696. PMID: 20823226, PMCID: PMC2944759, DOI: 10.1073/pnas.1006083107.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBrainCell DeathCell LineDopamineGene Knockout TechniquesHumansIn Vitro TechniquesMiceMice, KnockoutMolecular Sequence DataMutationNeuronsParkinson DiseasePC12 CellsPhosphorylationProto-Oncogene Proteins c-ablRatsRecombinant Fusion ProteinsStress, PhysiologicalUbiquitinationUbiquitin-Protein LigasesConceptsParkinson's diseaseTreatment of PDSTI-571Postmortem PD brainsSporadic Parkinson's diseaseC-AblProtective functionNonreceptor tyrosine kinase c-AblMPTP intoxicationUbiquitin E3 ligase activityNeuroprotective approachesPD brainsSubstantia nigraDopaminergic neurotoxinProtective effectProtein type 2Subsequent neurotoxicityNervous systemType 2Parkin inactivationAutosomal recessive Parkinson's diseaseConditional knockoutKinase inhibitorsRecessive Parkinson's diseaseTyrosine kinase c-AblSynaptic Clustering of PSD-95 Is Regulated by c-Abl through Tyrosine Phosphorylation
de Arce K, Varela-Nallar L, Farias O, Cifuentes A, Bull P, Couch BA, Koleske AJ, Inestrosa NC, Alvarez AR. Synaptic Clustering of PSD-95 Is Regulated by c-Abl through Tyrosine Phosphorylation. Journal Of Neuroscience 2010, 30: 3728-3738. PMID: 20220006, PMCID: PMC2872795, DOI: 10.1523/jneurosci.2024-09.2010.Peer-Reviewed Original ResearchConceptsPSD-95Protein postsynaptic density protein 95Postsynaptic density protein 95PSD-95 clusteringHippocampal neuron culturesFirst postnatal weekC-AblC-Abl levelsPresynaptic markersTyrosine phosphorylationRat hippocampusPostnatal weekPostsynaptic sitesSynaptic clusteringNeuron culturesSynaptic functionC-Abl kinase activityReduced synapsesSynapse formationPostsynaptic compartmentsBrain synapsesGenetic inhibitionSynapsesTyrosine kinaseC-Abl tyrosine kinase
2009
Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine
Gourley SL, Koleske AJ, Taylor JR. Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 16859-16864. PMID: 19805386, PMCID: PMC2742404, DOI: 10.1073/pnas.0902286106.Peer-Reviewed Original ResearchConceptsDopamine D2 receptor levelsLocomotor depressant actionsD2 receptor levelsWild-type micePsychomotor stimulant actionDendritic simplificationAntagonist haloperidolStimulant actionCocaine exposureCortical axonsDendritic arborsReceptor levelsCocaine administrationSynaptic pruningDendrite stabilizationNeuropsychiatric disordersArg inhibitionMiceNormal sensitivityDendritic refinementCytoskeletal stabilizationCocaineAdolescenceReversal taskRhoA GTPase
2008
T cell survival and function requires the c-Abl tyrosine kinase
Silberman I, Sionov RV, Zuckerman V, Haupt S, Goldberg Z, Strasser A, Ben-Sasson ZS, Baniyash M, Koleske AJ, Haupt Y. T cell survival and function requires the c-Abl tyrosine kinase. Cell Cycle 2008, 7: 3847-3857. PMID: 19098427, PMCID: PMC3407662, DOI: 10.4161/cc.7.24.7267.Peer-Reviewed Original ResearchConceptsT cellsThymic atrophyT cell numbersAnti-tumor antibodiesAdult T-cellT cell functionT cell survivalDeficient T cellsTumor cell killingLck-Cre transgeneSyngeneic tumorsCell-autonomous roleEarly deathImmune systemIncreased susceptibilityMiceImpaired abilityCell functionAtrophyCell killingCell numberSurvivalOxidative stress stimuliCell survivalRole of AblThe c-Abl tyrosine kinase regulates actin remodeling at the immune synapse
Huang Y, Comiskey EO, Dupree RS, Li S, Koleske AJ, Burkhardt JK. The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse. Blood 2008, 112: 111-119. PMID: 18305217, PMCID: PMC2435682, DOI: 10.1182/blood-2007-10-118232.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAnimalsCells, CulturedHumansInterleukin-2Jurkat CellsLymphocyte ActivationMiceMice, KnockoutPhosphorylationProtein BindingProteinsProto-Oncogene Proteins c-ablPseudopodiaReceptors, Antigen, T-CellSignal TransductionT-LymphocytesTranscription, GeneticWiskott-Aldrich Syndrome Protein FamilyConceptsC-AblImmune synapseActin responseC-Abl nonreceptor tyrosine kinaseT cell activationTyrosine kinaseC-Abl tyrosine kinaseC-Abl bindsActin regulatory proteinsNonreceptor tyrosine kinaseChemokine-induced T cell migrationT cell receptor engagementSH2 domainActin dynamicsActin reorganizationTyrosine phosphorylationRegulatory proteinsActin polymerizationDownstream eventsNormal localizationConditional knockout miceCoordinate actionReceptor engagementKinaseLamellipodial spreading
2007
Defective T Cell Development and Function in the Absence of Abelson Kinases
Gu JJ, Zhang N, He YW, Koleske AJ, Pendergast AM. Defective T Cell Development and Function in the Absence of Abelson Kinases. The Journal Of Immunology 2007, 179: 7334-7343. PMID: 18025176, DOI: 10.4049/jimmunol.179.11.7334.Peer-Reviewed Original ResearchConceptsT cell developmentT cellsMutant miceCell-autonomous roleT cell-dependent AgCD8 T cellsListeria monocytogenes infectionT cell expansionCell developmentNumber of thymocytesT cell functionDouble-positive stageDouble-negative populationDefective T cell developmentConditional knockout miceT cells resultsNull T cellsTCR-induced signalingCytokine productionMonocytogenes infectionAb productionKnockout miceThymocyte proliferationConditional deletionMiceInhibition of Rho via Arg and p190RhoGAP in the Postnatal Mouse Hippocampus Regulates Dendritic Spine Maturation, Synapse and Dendrite Stability, and Behavior
Sfakianos MK, Eisman A, Gourley SL, Bradley WD, Scheetz AJ, Settleman J, Taylor JR, Greer CA, Williamson A, Koleske AJ. Inhibition of Rho via Arg and p190RhoGAP in the Postnatal Mouse Hippocampus Regulates Dendritic Spine Maturation, Synapse and Dendrite Stability, and Behavior. Journal Of Neuroscience 2007, 27: 10982-10992. PMID: 17928439, PMCID: PMC6672862, DOI: 10.1523/jneurosci.0793-07.2007.Peer-Reviewed Original ResearchConceptsDendritic spine maturationDendritic regressionSpine maturationDendritic spinesNormal morphological maturationDendritic spine lossPostnatal day 21Late postnatal developmentPostnatal mouse hippocampusDendrite stabilityPyramidal dendritesSpine lossSynaptic refinementProgressive deficitsHippocampal synapsesMature neuronsArbor developmentInhibitory pathwaysMouse hippocampusDendrite arborsDay 21Postnatal developmentMorphological maturationDendritic branchesDendrite morphogenesisUse of a Chemical Genetic Technique To Identify Myosin IIB as a Substrate of the Abl-Related Gene (Arg) Tyrosine Kinase
Boyle SN, Koleske AJ. Use of a Chemical Genetic Technique To Identify Myosin IIB as a Substrate of the Abl-Related Gene (Arg) Tyrosine Kinase. Biochemistry 2007, 46: 11614-11620. PMID: 17892306, DOI: 10.1021/bi701119s.Peer-Reviewed Original ResearchConceptsPutative substratesMyosin IIBGene Tyrosine KinaseUnnatural ATP analoguesProtein substrate specificityPhosphotyrosine-containing proteinsSer/ThrAbl/ArgChemical-genetic techniqueCell morphogenesisKinase substrateDirect substrateFamily kinasesTyrosine phosphorylationSubstrate specificityGenetic techniquesNucleotide specificityMolecular mechanismsTyrosine kinaseK-252aUnexpected high levelATP analogGene kinaseKinaseABL
2005
Integrin-Mediated Dendrite Branch Maintenance Requires Abelson (Abl) Family Kinases
Moresco EM, Donaldson S, Williamson A, Koleske AJ. Integrin-Mediated Dendrite Branch Maintenance Requires Abelson (Abl) Family Kinases. Journal Of Neuroscience 2005, 25: 6105-6118. PMID: 15987940, PMCID: PMC6725048, DOI: 10.1523/jneurosci.1432-05.2005.Peer-Reviewed Original ResearchConceptsCortical dendritesPostnatal day 21Nervous system functionDendrite lossCortical neuronsSemaphorin 7ADay 21Arg kinase activityArbor sizeMouse brainArbor structureDendrite maintenanceEarly adulthoodNeurite branchingTyrosine kinaseNeurite branchesDendritesNonreceptor tyrosine kinaseIntegrin receptorsCritical determinantLaminin-1System functionKinase activityBranch dynamicsDendrite branches