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
2022
Atypical nuclear envelope condensates linked to neurological disorders reveal nucleoporin-directed chaperone activities
Prophet SM, Rampello AJ, Niescier RF, Gentile JE, Mallik S, Koleske AJ, Schlieker C. Atypical nuclear envelope condensates linked to neurological disorders reveal nucleoporin-directed chaperone activities. Nature Cell Biology 2022, 24: 1630-1641. PMID: 36302970, PMCID: PMC10041656, DOI: 10.1038/s41556-022-01001-y.Peer-Reviewed Original ResearchAutoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants
Bircher JE, Corcoran EE, Lam TT, Trnka MJ, Koleske AJ. Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants. Journal Of Biological Chemistry 2022, 298: 102361. PMID: 35963430, PMCID: PMC9467883, DOI: 10.1016/j.jbc.2022.102361.Peer-Reviewed Original ResearchConceptsSpectrin repeatsGEF1 domainPleckstrin homology regionExchange factor domainKey regulatory mechanismCytoskeletal regulatory proteinsSmall GTPase Rac1Autoinhibitory constraintsAccessory domainsNeurodevelopmental disordersGEF activityMultiple neurodevelopmental disordersKinase domainHomology regionProtein TrioGTPase Rac1Regulatory proteinsRegulatory mechanismsFactor domainSRS-6Genetic variantsGef1Disease variantsEnzymatic activityBio-Layer InterferometryControl of Synapse Structure and Function by Actin and Its Regulators
Gentile JE, Carrizales MG, Koleske AJ. Control of Synapse Structure and Function by Actin and Its Regulators. Cells 2022, 11: 603. PMID: 35203254, PMCID: PMC8869895, DOI: 10.3390/cells11040603.Peer-Reviewed Original ResearchConceptsActin poolsOrganization of proteinsSynaptic actinOrganization of actinDisease risk genesKey neuronal functionsPost-synaptic compartmentsActin regulatorsDynamic regulationActin filamentsWhole-exome sequencingRisk genesIon channelsGenetic variantsActinRegulatorNeuronal functionSynapse structureExome sequencingPostsynaptic dendritic spinesKey functionsSpecialized junctionsGenesPresynaptic axon terminalsAxon terminals
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 kinaseTrio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts
Bircher JE, Koleske AJ. Trio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts. Journal Of Cell Science 2021, 134: jcs248393. PMID: 33568469, PMCID: PMC7888718, DOI: 10.1242/jcs.248393.Peer-Reviewed Original ResearchConceptsFamily proteinsCellular contextProtein-protein interaction domainsHuman diseasesProtein trafficking pathwaysLarge multidomain proteinCell surface receptorsTrio proteinsUNC-73Cell morphogenesisProtein traffickingTrafficking pathwaysMultidomain proteinsInteraction domainInteraction partnersKey regulatorBiological contextTissue organizationCell migrationSurface receptorsProteinTrio familiesRecent discoveryMorphogenesisRegulator
2020
Two-color nanoscopy of organelles for extended times with HIDE probes
Chu L, Tyson J, Shaw JE, Rivera-Molina F, Koleske AJ, Schepartz A, Toomre DK. Two-color nanoscopy of organelles for extended times with HIDE probes. Nature Communications 2020, 11: 4271. PMID: 32848153, PMCID: PMC7450044, DOI: 10.1038/s41467-020-17859-1.Peer-Reviewed Original ResearchNeural 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
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
2018
Noonan 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 oocytesAnalysis 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
The vascular endothelial specific IL-4 receptor alpha–ABL1 kinase signaling axis regulates the severity of IgE-mediated anaphylactic reactions
Yamani A, Wu D, Waggoner L, Noah T, Koleske AJ, Finkelman F, Hogan SP. The vascular endothelial specific IL-4 receptor alpha–ABL1 kinase signaling axis regulates the severity of IgE-mediated anaphylactic reactions. Journal Of Allergy And Clinical Immunology 2017, 142: 1159-1172.e5. PMID: 29157947, PMCID: PMC5957775, DOI: 10.1016/j.jaci.2017.08.046.Peer-Reviewed Original ResearchConceptsIgE-mediated anaphylactic reactionsAnaphylactic reactionsFluid extravasationIL-4RαBarrier dysfunctionIL-4Food-induced anaphylactic reactionsIgE-induced anaphylaxisFood-induced anaphylaxisIgE-mediated anaphylaxisIL-4 receptor α chainIgE-mediated reactionsTreatment of miceSevere anaphylactic reactionsSeverity of anaphylaxisABL kinase inhibitor imatinibKinase inhibitor imatinibReceptor α chainVe cell linesVenous vasodilatationOral antigenHypovolemic shockInhibitor imatinibAnaphylaxisVe cellsNeurodevelopmental 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 understandingRac1ActivityLong‐Term Live‐Cell STED Nanoscopy of Primary and Cultured Cells with the Plasma Membrane HIDE Probe DiI‐SiR
Thompson AD, Omar MH, Rivera‐Molina F, Xi Z, Koleske AJ, Toomre DK, Schepartz A. Long‐Term Live‐Cell STED Nanoscopy of Primary and Cultured Cells with the Plasma Membrane HIDE Probe DiI‐SiR. Angewandte Chemie International Edition 2017, 56: 10408-10412. PMID: 28679029, PMCID: PMC5576494, DOI: 10.1002/anie.201704783.Peer-Reviewed Original ResearchBrain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity
Miller MB, Yan Y, Machida K, Kiraly DD, Levy AD, Wu YI, Lam TT, Abbott T, Koleske AJ, Eipper BA, Mains RE. Brain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity. ACS Chemical Neuroscience 2017, 8: 1554-1569. PMID: 28418645, PMCID: PMC5517348, DOI: 10.1021/acschemneuro.7b00076.Peer-Reviewed Original ResearchConceptsLong-term potentiationCalpain sensitivityEffects of cocaineRat nucleus accumbensAdult rat nucleus accumbensRho GDP/GTP exchange factorRegion-specific effectsChronic cocaineNucleus accumbensSynaptic functionBrain regionsKALRN geneSpine morphologyPrefrontal cortexKal7CocainePotentiationFunctional significanceCalpainPhosphorylationPhosphorylated 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
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 networksTAZ