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
2021
Platelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation
Wu K, Wu H, Lyu W, Kim Y, Furdui CM, Anderson KS, Koleske AJ. Platelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation. Journal Of Biological Chemistry 2021, 297: 100883. PMID: 34144039, PMCID: PMC8259415, DOI: 10.1016/j.jbc.2021.100883.Peer-Reviewed Original ResearchConceptsAbl family kinasesFamily kinasesPlatelet-derived growth factor receptor betaGrowth factor receptor betaAbl familySrc homology 2 domainSrc homology 3 domainDiverse cellular stimuliPost-translational modificationsN-terminal halfNonreceptor tyrosine kinaseMultiple novel sitesAutoinhibited conformationSrc homologyCytoskeleton organizationCytoplasmic domainCellular stimuliKinase domainGrowth factor receptorReceptor betaKinase activityMolecular mechanismsTyrosine kinaseDirect bindingKinaseAbl2:Cortactin Interactions Regulate Dendritic Spine Stability via Control of a Stable Filamentous Actin Pool
Shaw JE, Kilander MBC, Lin YC, Koleske AJ. Abl2:Cortactin Interactions Regulate Dendritic Spine Stability via Control of a Stable Filamentous Actin Pool. Journal Of Neuroscience 2021, 41: 3068-3081. PMID: 33622779, PMCID: PMC8026353, DOI: 10.1523/jneurosci.2472-20.2021.Peer-Reviewed Original ResearchConceptsDendritic spine stabilityDendritic spinesSpine stabilityTonic increaseSubset of spinesSexes of miceMost excitatory synapsesCortactin interactionsGluN2B levelsSpine densitySpine lossArg nonreceptor tyrosine kinaseKinetically distinct poolsExcitatory synapsesHippocampal neuronsSynaptic activitySpine enlargementSpineSpine sizeSpine actinActivity-dependent spine enlargementSpine shapeStructural plasticityDistinct poolsTyrosine kinase
2020
Neural Stem Cells Direct Axon Guidance via Their Radial Fiber Scaffold
Kaur N, Han W, Li Z, Madrigal MP, Shim S, Pochareddy S, Gulden FO, Li M, Xu X, Xing X, Takeo Y, Li Z, Lu K, Imamura Kawasawa Y, Ballester-Lurbe B, Moreno-Bravo JA, Chédotal A, Terrado J, Pérez-Roger I, Koleske AJ, Sestan N. Neural Stem Cells Direct Axon Guidance via Their Radial Fiber Scaffold. Neuron 2020, 107: 1197-1211.e9. PMID: 32707082, PMCID: PMC7529949, DOI: 10.1016/j.neuron.2020.06.035.Peer-Reviewed Original ResearchConceptsNeural stem cellsDendritic spine formationNeural circuit formationRadial glia-like neural stem cellsMedial ganglionic eminenceRadial fibersAxon guidanceStem cellsCorticospinal neuronsGlobus pallidusMacroglial cellsGanglionic eminenceCircuit formationVentricular zoneSpine formationRnd3/RhoENeuronsMidline crossingExpression of Rnd3Rho GTPaseCellsExpressionUnexpected roleAtypical Rho GTPaseRnd3ABL1, Overexpressed in Hepatocellular Carcinomas, Regulates Expression of NOTCH1 and Promotes Development of Liver Tumors in Mice
Wang F, Hou W, Chitsike L, Xu Y, Bettler C, Perera A, Bank T, Cotler SJ, Dhanarajan A, Denning MF, Ding X, Breslin P, Qiang W, Li J, Koleske AJ, Qiu W. ABL1, Overexpressed in Hepatocellular Carcinomas, Regulates Expression of NOTCH1 and Promotes Development of Liver Tumors in Mice. Gastroenterology 2020, 159: 289-305.e16. PMID: 32171747, PMCID: PMC7387191, DOI: 10.1053/j.gastro.2020.03.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, HepatocellularCell Line, TumorDatasets as TopicDisease Models, AnimalFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansKaplan-Meier EstimateLiverLiver NeoplasmsMaleMicePhosphorylationPrognosisProto-Oncogene MasProto-Oncogene Proteins c-ablProto-Oncogene Proteins c-mycPyrimidinesReceptor, Notch1Xenograft Model Antitumor AssaysConceptsShorter survival timeLiver tumorsExpression of Notch1Hepatocellular carcinomaHuman HCC cellsHCC cellsXenograft tumorsSurvival timeExpression of MYCLiver tissueTreatment of HCCAlbumin-Cre miceNon-tumor liver tissuesABL proto-oncogene 1Nontumor liver tissuesHuman HCC specimensHuh7 HCC cellsHepatocyte-specific disruptionHCC tissue microarrayProto-oncogene 1HCC cell linesShort hairpin RNACancer Genome AtlasKnockdown of Notch1Tumor levels
2019
Regulation of MT dynamics via direct binding of an Abl family kinase
Hu Y, Lyu W, Lowery LA, Koleske AJ. Regulation of MT dynamics via direct binding of an Abl family kinase. Journal Of Cell Biology 2019, 218: 3986-3997. PMID: 31699690, PMCID: PMC6891085, DOI: 10.1083/jcb.201812144.Peer-Reviewed Original ResearchConceptsAbl family kinasesC-terminal halfFamily kinasesMT dynamicsMT growthTubulin C-terminal tailsC-terminal tailStable reexpressionEssential regulatorCell shapeBinds microtubulesMT polymerizationAbl kinaseGenetic studiesDirect bindingFunctional interactionKinaseMicrotubulesABL2ReexpressionMT behaviorBindingRegulatorProteinGrowthIntegrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis
Yun S, Hu R, Schwaemmle ME, Scherer AN, Zhuang Z, Koleske AJ, Pallas DC, Schwartz MA. Integrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis. Journal Of Clinical Investigation 2019, 129: 4863-4874. PMID: 31408443, PMCID: PMC6819111, DOI: 10.1172/jci127692.Peer-Reviewed Original ResearchConceptsPP2A regulatory subunit B55αTranscription factor YAPActive PDEComplex assemblyAdapter rolePDE4D5B55αIntegrin α5EC phenotypeCell functionInflammatory signalingAthero-prone regionsActivationComplexesPP2AInflammatory activationWidespread consequencesDephosphorylationProteomicsVascular remodelingPlaque sizeAtherosclerotic plaque sizeSignalingYAPRegulatesTrio 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
2018
Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension
Zhang K, Lyu W, Yu J, Koleske AJ. Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension. Molecular Biology Of The Cell 2018, 29: 2863-2873. PMID: 30256707, PMCID: PMC6249870, DOI: 10.1091/mbc.e18-01-0044.Peer-Reviewed Original ResearchConceptsCytoskeletal interactionsLamellipodium extensionTotal internal reflection fluorescence microscopyActin-rich structuresActin wavesActin-rich protrusionsN-terminal halfC-terminal halfNonreceptor tyrosine kinaseReflection fluorescence microscopyFoci colocalizeComplementation analysisLamellipodia protrusionKnockout cellsLamellipodium tipActin filament stabilizerCell shapeBind actinTyrosine kinaseCortactinABL2Fluorescence microscopyIntegrin β3High spatiotemporal resolutionPaxillinNoonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function
Levy AD, Xiao X, Shaw JE, Devi S, Katrancha SM, Bennett AM, Greer CA, Howe JR, Machida K, Koleske AJ. Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function. Cell Reports 2018, 24: 1523-1535. PMID: 30089263, PMCID: PMC6234505, DOI: 10.1016/j.celrep.2018.07.006.Peer-Reviewed Original ResearchConceptsTyrosine phosphatase SHP2Noonan syndromePhosphatase SHP2Regulatory proteinsSHP2Recombinant GluN1Nck2Receptor functionNMDA receptor functionNMDAR functionGluN2B functionMutationsNMDAR dysfunctionNeuron functionNS miceGluN1ProteinAllelesNMDA receptorsDiheteromersReceptor kineticsReduced contributionsFunctionHyperactivationMiceTransient inhibition of p53 homologs protects ovarian function from two distinct apoptotic pathways triggered by anticancer therapies
Kim SY, Nair DM, Romero M, Serna VA, Koleske AJ, Woodruff TK, Kurita T. Transient inhibition of p53 homologs protects ovarian function from two distinct apoptotic pathways triggered by anticancer therapies. Cell Death & Differentiation 2018, 26: 502-515. PMID: 29988075, PMCID: PMC6370889, DOI: 10.1038/s41418-018-0151-2.Peer-Reviewed Original ResearchConceptsDistinct apoptotic pathwaysDNA damage responseDamage-induced apoptosisTemporary repressionPhosphorylation of ATMOocyte-specific deletionActivation/phosphorylationKinase inhibitorsCDDP-induced apoptosisDamage responseMultiple kinasesMolecular basisP53 homologApoptotic pathwayNovel pathwayAbl kinase inhibitorsOvarian functionApoptosisPathwayRepressionTAp63αPhosphorylationOocytesATRImmature oocytesCortactin stabilization of actin requires actin-binding repeats and linker, is disrupted by specific substitutions, and is independent of nucleotide state
Scherer AN, Anand NS, Koleske AJ. Cortactin stabilization of actin requires actin-binding repeats and linker, is disrupted by specific substitutions, and is independent of nucleotide state. Journal Of Biological Chemistry 2018, 293: 13022-13032. PMID: 29929984, PMCID: PMC6109930, DOI: 10.1074/jbc.ra118.004068.Peer-Reviewed Original ResearchConceptsHematopoietic cell-specific Lyn substrate 1Nucleotide stateActin bindingActin filamentsTotal internal reflection fluorescence microscopyActin-binding proteins cortactinActin cosedimentation assaysActin-rich structuresHigh-affinity actin bindingADP-actin filamentsReflection fluorescence microscopyAdjacent linker regionActin filament bindingArp2/3 complexCortactin repeatsCellular functionsActin stabilityCosedimentation assaysActin stabilizationProtein cortactinLamellipodial protrusionGTPase regulatorFilament depolymerizationLinker regionActin depolymerizationA Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation
Jacobsen FA, Scherer AN, Mouritsen J, Bragadóttir H, Thomas Bäckström B, Sardar S, Holmberg D, Koleske AJ, Andersson Å. A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation. Journal Of Neuroimmune Pharmacology 2018, 13: 265-276. PMID: 29550892, PMCID: PMC5928183, DOI: 10.1007/s11481-018-9783-8.Peer-Reviewed Original ResearchConceptsMultiple sclerosisExperimental autoimmune encephalomyelitis (EAE) modelT cell receptorCongenic mouse strainsExperimental neuroinflammationInflammation pathogenesisMyelin antigensEAE developmentExperimental arthritisAutoimmune responseImmune cellsDisease susceptibility factorsCongenic miceLymphocyte activationPharmacological inhibitionAbl kinaseSclerosisSusceptibility factorsMouse strainsDegenerative diseasesPotential drug targetsMouse genetic locusSingle nucleotide polymorphismsDisease etiologyAmino acid changesAnalysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase
Wang Z, Kim MS, Martinez-Ferrando I, Koleske A, Pandey A, Cole P. Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase. Biochemistry 2018, 57: 1390-1398. PMID: 29341593, PMCID: PMC5906802, DOI: 10.1021/acs.biochem.7b01158.Peer-Reviewed Original ResearchConceptsProtein kinaseNonreceptor tyrosine kinases AblMass spectrometry-based quantitative proteomicsNovel putative substratesTyrosine kinase AblCellular tyrosine phosphorylationExtracellular growth factorsChemical rescue approachIntracellular signal transductionQuantitative phosphoproteomicsUnanticipated functionCellular physiologyGrowth factorPhosphorylation sitesPutative substratesDirect substrateDownstream substratesSignal transductionReceptor kinaseQuantitative proteomicsTyrosine phosphorylationActive Abl kinasesAbl kinaseChemical rescueKinase
2017
Corticosteroid-induced dendrite loss and behavioral deficiencies can be blocked by activation of Abl2/Arg kinase
Shapiro LP, Omar MH, Koleske AJ, Gourley SL. Corticosteroid-induced dendrite loss and behavioral deficiencies can be blocked by activation of Abl2/Arg kinase. Molecular And Cellular Neuroscience 2017, 85: 226-234. PMID: 29107098, PMCID: PMC5767942, DOI: 10.1016/j.mcn.2017.10.007.Peer-Reviewed Original ResearchConceptsCorticosterone exposureHippocampal CA1 pyramidal neuronsStressor exposureArbor structureCA1 pyramidal neuronsAnhedonic-like behaviorClassical neurotransmitter systemsSpecific brain regionsMental health concernsDendrite lossPyramidal neuronsStress-related illnessesArg nonreceptor tyrosine kinaseNeuronal remodelingNeurotransmitter systemsNeural degenerationBehavioral abnormalitiesTrigger pointsCognitive declineBrain regionsKey next stepHealth concernKey mediatorMental healthPharmacological compoundsCNS 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 networksTAZDifferential expression of cytoskeletal regulatory factors in the adolescent prefrontal cortex: Implications for cortical development
Shapiro LP, Parsons RG, Koleske AJ, Gourley SL. Differential expression of cytoskeletal regulatory factors in the adolescent prefrontal cortex: Implications for cortical development. Journal Of Neuroscience Research 2016, 95: 1123-1143. PMID: 27735056, PMCID: PMC5352542, DOI: 10.1002/jnr.23960.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAge FactorsAnalysis of VarianceAnimalsBrain-Derived Neurotrophic FactorCytoskeletonDendritic SpinesFemaleGene Expression Regulation, DevelopmentalHumansIntegrin beta1MaleMembrane GlycoproteinsMiceMice, TransgenicNeural PathwaysNeuronsPrefrontal CortexReceptor, trkBSignal TransductionSynapsesSynaptophysinConceptsPrefrontal cortexDendritic spinesTropomyosin-related kinase receptor BDifferent adolescent agesKinase receptor BPrevalence of depressionMental health disordersDeep-layer excitatory neuronsRho kinase 2TrkB levelsVentral hippocampusOrbital prefrontal cortexAge-related differencesPsychiatric illnessReceptor BExcitatory neuronsPostnatal brainHealth disordersAnatomical connectionsNeuronal structuresWestern blottingAdolescent ageEarly adulthoodDramatic structural reorganizationPFC subregions