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 ResearchMeSH KeywordsActin CytoskeletonActinsAnimalsAnimals, NewbornCortactinDendritic SpinesFemaleHEK293 CellsHumansMaleMiceMice, Inbred BALB CProtein BindingProtein-Tyrosine KinasesConceptsDendritic 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
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 behaviorBindingRegulatorProteinGrowth
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 ResearchMeSH KeywordsActin CytoskeletonActinsAnimalsCell MovementCell ShapeChlorocebus aethiopsCortactinCOS CellsCytoskeletonFibroblastsMiceProtein BindingProtein-Tyrosine KinasesPseudopodiaConceptsCytoskeletal 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 resolutionPaxillinA 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 ResearchMeSH KeywordsAnimalsEncephalomyelitis, Autoimmune, ExperimentalMiceMice, Mutant StrainsPolymorphism, Single NucleotideProtein-Tyrosine KinasesConceptsMultiple 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 changes
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 mechanismsΑ5LamininNeurotransmissionPhosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in invasive breast cancer cells
Rosenberg BJ, Gil-Henn H, Mader CC, Halo T, Yin T, Condeelis J, Machida K, Wu YI, Koleske AJ. Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in invasive breast cancer cells. Molecular Biology Of The Cell 2017, 28: 1347-1360. PMID: 28356423, PMCID: PMC5426849, DOI: 10.1091/mbc.e16-12-0885.Peer-Reviewed Original ResearchConceptsInvasive breast cancer cellsInvadopodium maturationBreast cancer cellsActin nucleation-promoting factorCancer cellsSH2 domain bindsHuman SH2 domainsMatrix degradationNucleation-promoting factorsGuanine nucleotide exchange factor Vav2Actin-rich protrusionsSubsequent cell invasionExchange factor Vav2Active Rac3Invasive MDA-MB-231 breast cancer cellsMDA-MB-231 breast cancer cellsInvadopodial functionSH2 domainDomain bindsExchange factorKinase cascadeCortactin phosphorylationActin polymerizationMutant formsInvadopodia
2016
Disruption 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 plasticityThe Src kinases Hck, Fgr and Lyn activate Arg to facilitate IgG-mediated phagocytosis and Leishmania infection
Wetzel DM, Rhodes EL, Li S, McMahon-Pratt D, Koleske AJ. The Src kinases Hck, Fgr and Lyn activate Arg to facilitate IgG-mediated phagocytosis and Leishmania infection. Journal Of Cell Science 2016, 129: 3130-3143. PMID: 27358479, PMCID: PMC5004897, DOI: 10.1242/jcs.185595.Peer-Reviewed Original ResearchMeSH KeywordsAniline CompoundsAnimalsCytokinesDisease Models, AnimalImatinib MesylateImmunoglobulin GLeishmaniaLeishmaniasisMacrophagesMiceModels, BiologicalNitrilesParasitesPhagocytosisPhosphorylationProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-hckPyrimidinesQuinolinesRAW 264.7 CellsSignal TransductionSrc-Family KinasesConceptsAmastigote uptakeObligate intracellular parasite LeishmaniaImmunoglobulin-mediated phagocytosisIntracellular parasite LeishmaniaNovel therapeutic strategiesPersistence of infectionLeishmania infectionIgG-mediated phagocytosisTherapeutic strategiesFc receptorsSmall molecule inhibitorsArg activationDisease severityParasite burdenPrimary macrophagesMacrophagesKinase inhibitorsLeishmaniasisHuman hostDevastating diseaseInfectionParasite LeishmaniaSrc family kinasesPhagocytosisLeishmania
2015
Structure of the ABL2/ARG kinase in complex with dasatinib
Ha BH, Simpson MA, Koleske AJ, Boggon TJ. Structure of the ABL2/ARG kinase in complex with dasatinib. Acta Crystallographica Section F: Structural Biology Communications 2015, 71: 443-448. PMID: 25849507, PMCID: PMC4388181, DOI: 10.1107/s2053230x15004793.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDasatinibHumansMiceProtein Kinase InhibitorsProtein Structure, SecondaryProtein Structure, TertiaryProtein-Tyrosine KinasesConceptsT-cell acute lymphoblastic leukemiaActivation loop tyrosinesABL kinase activationGlycine-rich P-loopCell morphogenesisCo-crystal structureBreakpoint cluster regionCellular functionsArg genesCatalytic domainAbl familyArg kinaseP-loopKinase activationBiological roleOpen conformationTyrosine kinaseAbl kinaseKinaseGenesKinase inhibitorsABL1 geneArgCluster regionTyrosine kinase inhibitorsDirect Interactions with the Integrin β1 Cytoplasmic Tail Activate the Abl2/Arg Kinase*
Simpson MA, Bradley WD, Harburger D, Parsons M, Calderwood DA, Koleske AJ. Direct Interactions with the Integrin β1 Cytoplasmic Tail Activate the Abl2/Arg Kinase*. Journal Of Biological Chemistry 2015, 290: 8360-8372. PMID: 25694433, PMCID: PMC4375489, DOI: 10.1074/jbc.m115.638874.Peer-Reviewed Original ResearchConceptsIntegrin β1 cytoplasmic tailExtracellular matrix adhesion receptorsSrc homology domainFibroblast cell motilityIntegrin β1Β1 cytoplasmic tailMembrane-proximal segmentAdhesion complex formationMatrix adhesion receptorsNonreceptor tyrosine kinaseArg kinase activityArg nonreceptor tyrosine kinaseCancer cell invasivenessHomology domainActin cytoskeletonCytoplasmic tailCytoskeletal remodelingDendrite morphogenesisTyr-783Kinase domainPhosphorylated regionAbl familyΒ1 tailArg kinaseCell motility
2014
Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin*
Courtemanche N, Gifford SM, Simpson MA, Pollard TD, Koleske AJ. Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin*. Journal Of Biological Chemistry 2014, 290: 4038-4046. PMID: 25540195, PMCID: PMC4326814, DOI: 10.1074/jbc.m114.608117.Peer-Reviewed Original Research
2013
Arg kinase signaling in dendrite and synapse stabilization pathways: Memory, cocaine sensitivity, and stress
Kerrisk ME, Koleske AJ. Arg kinase signaling in dendrite and synapse stabilization pathways: Memory, cocaine sensitivity, and stress. The International Journal Of Biochemistry & Cell Biology 2013, 45: 2496-2500. PMID: 23916785, PMCID: PMC3797846, DOI: 10.1016/j.biocel.2013.07.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCocaineDendritesHumansMemoryProtein-Tyrosine KinasesSignal TransductionStress, PsychologicalSynapsesConceptsNeuronal actin cytoskeletonPhosphorylation of substratesNonreceptor tyrosine kinaseArg nonreceptor tyrosine kinaseActin cytoskeletonPostnatal mouse brainDendritic spinesArg kinaseMolecular mechanismsF-actinTyrosine kinaseSignaling pathwaysPostnatal day 21Synapse stabilityIntegrin α3β1KinaseNeurodegenerative diseasesNeuronal remodelingTherapeutic approachesCocaine sensitivityStabilization pathwayDay 21Arbor sizeMouse brainArgβ1 integrin regulates Arg to promote invadopodial maturation and matrix degradation
Beaty BT, Sharma VP, Bravo-Cordero JJ, Simpson MA, Eddy RJ, Koleske AJ, Condeelis J. β1 integrin regulates Arg to promote invadopodial maturation and matrix degradation. Molecular Biology Of The Cell 2013, 24: 1661-1675. PMID: 23552693, PMCID: PMC3667720, DOI: 10.1091/mbc.e12-12-0908.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsActinsCell Line, TumorCell MovementCortactinExtracellular MatrixGene Expression Regulation, NeoplasticHumansIntegrin beta1PhosphorylationProtein BindingProtein MultimerizationProtein-Tyrosine KinasesPseudopodiaRNA, Small InterferingSignal TransductionTyrosineConceptsΒ1 integrinBarbed end formationInvasive membrane protrusionsMatrix degradationΒ1 integrin activationMature invadopodiaInvadopodial functionMetastatic human breast cancer cellsMembrane protrusionsExtracellular matrix degradationCortactin phosphorylationTyrosine 421InvadopodiaIntegrin activationMatrix proteolysisHuman breast cancer cellsThree-dimensional matrixPrecursor maturationBreast cancer cellsMetastatic tumor cellsIntegrinsCancer cellsPhosphorylationMaturationFundamental roleAbl2/Arg Controls Dendritic Spine and Dendrite Arbor Stability via Distinct Cytoskeletal Control Pathways
Lin YC, Yeckel MF, Koleske AJ. Abl2/Arg Controls Dendritic Spine and Dendrite Arbor Stability via Distinct Cytoskeletal Control Pathways. Journal Of Neuroscience 2013, 33: 1846-1857. PMID: 23365224, PMCID: PMC3711664, DOI: 10.1523/jneurosci.4284-12.2013.Peer-Reviewed Original Research
2012
Arg/Abl2 Modulates the Affinity and Stoichiometry of Binding of Cortactin to F‑Actin
MacGrath SM, Koleske AJ. Arg/Abl2 Modulates the Affinity and Stoichiometry of Binding of Cortactin to F‑Actin. Biochemistry 2012, 51: 6644-6653. PMID: 22849492, PMCID: PMC3556572, DOI: 10.1021/bi300722t.Peer-Reviewed Original ResearchConceptsStoichiometry of bindingF-actinTerminal calponin homology domainRecruitment of cortactinActin cosedimentation assaysArp2/3 complex activatorsCell edge protrusionActin network assemblyCalponin homology domainProtein-protein interactionsCortactin bindsHomology domainActin cytoskeletonArg CDeletion mutantsCosedimentation assaysFilamentous actinEdge protrusionComplex activatorActin binding propertiesCortactinActin filamentsNetwork assemblyDownstream effectsBindingThe 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 phagocytosisPhagocytosisReceptorsC3biInfectionLeishmaniasis
2011
An EGFR–Src–Arg–Cortactin Pathway Mediates Functional Maturation of Invadopodia and Breast Cancer Cell Invasion
Mader CC, Oser M, Magalhaes MA, Bravo-Cordero JJ, Condeelis J, Koleske AJ, Gil-Henn H. An EGFR–Src–Arg–Cortactin Pathway Mediates Functional Maturation of Invadopodia and Breast Cancer Cell Invasion. Cancer Research 2011, 71: 1730-1741. PMID: 21257711, PMCID: PMC3057139, DOI: 10.1158/0008-5472.can-10-1432.Peer-Reviewed Original ResearchConceptsBreast cancer cell invasionActin polymerizationCancer cell invasionInvadopodium maturationCell invasionCortactin phosphorylationEGFR-SrcExtracellular matrixTumor cell invasionInvadopodia functionV-SrcProtein cortactinEpidermal growth factorKnockdown cellsInvadopodiaFunctional maturationMaster switchSrc overexpressionCandidate therapeutic targetInvasive carcinoma cellsECM degradationNovel mechanismPhosphorylationNovel mediatorArg activation
2010
The Abl and Arg non‐receptor tyrosine kinases regulate different zones of stress fiber, focal adhesion, and contractile network localization in spreading fibroblasts
Peacock JG, Couch BA, Koleske AJ. The Abl and Arg non‐receptor tyrosine kinases regulate different zones of stress fiber, focal adhesion, and contractile network localization in spreading fibroblasts. Cytoskeleton 2010, 67: 666-675. PMID: 20737438, PMCID: PMC2955401, DOI: 10.1002/cm.20479.Peer-Reviewed Original ResearchConceptsCell peripheryPhosphorylated myosin light chainFocal adhesionsActomyosin contractilitySpatial regulationFocal adhesion dynamicsNon-receptor tyrosine kinaseAbl functionAdhesion dynamicsMutant cellsAbl familyFA formationStress fibersEdge protrusionMyosin light chainF-actinTyrosine kinaseRhoA activityInhibitory complexWT cellsArg functionAdhesive structuresCell migrationAdhesion elementsP120