2021
Abl2: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
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 resolutionPaxillinCortactin 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 depolymerization
2017
The repeat region of cortactin is intrinsically disordered in solution
Li X, Tao Y, Murphy JW, Scherer AN, Lam TT, Marshall AG, Koleske AJ, Boggon TJ. The repeat region of cortactin is intrinsically disordered in solution. Scientific Reports 2017, 7: 16696. PMID: 29196701, PMCID: PMC5711941, DOI: 10.1038/s41598-017-16959-1.Peer-Reviewed Original ResearchConceptsCortactin repeatsRepeat regionActin filamentsHydrogen-deuterium exchange mass spectrometryAdjacent helical regionsMulti-domain proteinsExchange mass spectrometryExtensive biophysical analysisCircular dichroismHydrophobic core regionSmall-angle X-ray scatteringBiophysical analysisHelical regionCortactinRepeatsSimilar copiesUnfolded peptidesProteinMotifSize exclusion chromatographyMass spectrometryFilamentsExclusion chromatographyX-ray scatteringRegionPhosphorylated 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
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 ResearchTwo 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
2013
β1 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 role
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 effectsBindingCortactin in cell migration and cancer at a glance
MacGrath SM, Koleske AJ. Cortactin in cell migration and cancer at a glance. Journal Of Cell Science 2012, 125: 1621-1626. PMID: 22566665, PMCID: PMC3346822, DOI: 10.1242/jcs.093781.Peer-Reviewed Original ResearchLysozyme contamination facilitates crystallization of a heterotrimeric cortactin–Arg–lysozyme complex
Liu W, MacGrath SM, Koleske AJ, Boggon TJ. Lysozyme contamination facilitates crystallization of a heterotrimeric cortactin–Arg–lysozyme complex. Acta Crystallographica Section F: Structural Biology Communications 2012, 68: 154-158. PMID: 22297987, PMCID: PMC3274391, DOI: 10.1107/s1744309111056132.Peer-Reviewed Original ResearchConceptsCrystal structure determinationNonreceptor tyrosine kinaseArg nonreceptor tyrosine kinaseHeterotrimeric complexSH3 domainMacromolecular crystallographersCrystallography approachStructure determinationTyrosine kinaseCocrystal structureMolecular replacementTrace amountsLysozyme complexStructure solutionProteinCortactinComplexesCrystallizationCrystallographersCocrystalsKinaseMotifAutomatic model buildingSequenceArg
2011
Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway
Magalhaes MA, Larson DR, Mader CC, Bravo-Cordero JJ, Gil-Henn H, Oser M, Chen X, Koleske AJ, Condeelis J. Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway. Journal Of Cell Biology 2011, 195: 903-920. PMID: 22105349, PMCID: PMC3257566, DOI: 10.1083/jcb.201103045.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsAdaptor Proteins, Signal TransducingCation Transport ProteinsCell Line, TumorCell Surface ExtensionsCortactinHumansHydrogen-Ion ConcentrationModels, BiologicalNeoplasm InvasivenessOncogene ProteinsPhosphorylationSodium-Hydrogen Exchanger 1Sodium-Hydrogen ExchangersConceptsCortactin phosphorylationCell invasionInvadopodia maturationCortactin tyrosine phosphorylationPH-dependent regulationInvasive protrusionsPH-dependent pathwayCofilin activityCofilin regulationTyrosine phosphorylationExchanger NHE1Cofilin activationPhosphorylationInvadopodiaProteolytic activityPrecise mechanismInvasionNHE1RegulationDynamic cyclePathwayMaturationTumor cellsNck1CofilinAn 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
Specific tyrosine phosphorylation sites on cortactin regulate Nck1-dependent actin polymerization in invadopodia
Oser M, Mader CC, Gil-Henn H, Magalhaes M, Bravo-Cordero JJ, Koleske AJ, Condeelis J. Specific tyrosine phosphorylation sites on cortactin regulate Nck1-dependent actin polymerization in invadopodia. Journal Of Cell Science 2010, 123: 3662-3673. PMID: 20971703, PMCID: PMC3037016, DOI: 10.1242/jcs.068163.Peer-Reviewed Original ResearchConceptsTyrosine phosphorylation sitesTumor cell invasionActin polymerizationPhosphorylation sitesCell invasionTyrosine 421Actin barbed endsPhosphorylation of tyrosineRegulatory switchSH2 domainMembrane protrusionsInvadopodiaCrucial residuesCortactinBarbed endsDirect bindingInvasive carcinoma cellsPhosphorylationNck1Carcinoma cellsFRET interactionsInvasionCellsPhosphotyrosineSites
2009
Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation
Oser M, Yamaguchi H, Mader CC, Bravo-Cordero JJ, Arias M, Chen X, DesMarais V, van Rheenen J, Koleske AJ, Condeelis J. Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. Journal Of Cell Biology 2009, 186: 571-587. PMID: 19704022, PMCID: PMC2733743, DOI: 10.1083/jcb.200812176.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsActin-Related Protein 2-3 ComplexActinsAdaptor Proteins, Signal TransducingAnimalsCell Line, TumorCortactinEpidermal Growth FactorExtracellular MatrixHumansMammary Neoplasms, AnimalMatrix Metalloproteinase 14Neoplasm InvasivenessOncogene Protein pp60(v-src)Oncogene ProteinsPhosphorylationProtein Structure, TertiaryRatsRecombinant Fusion ProteinsRNA, Small InterferingTyrosineWiskott-Aldrich Syndrome Protein, NeuronalConceptsInvadopodium assemblyActin polymerizationCortactin phosphorylationArp2/3 complex-dependent actin polymerizationArp2/3-dependent actin polymerizationComplex-dependent actin polymerizationBarbed end formationN-WASP activityCarcinoma cellsMembrane protrusionsEnd formationSevering activityInvadopodiaMaster switchActin filamentsBarbed endsCortactinInvasive carcinoma cellsMetastatic carcinoma cellsNovel mechanismPhosphorylationCofilinMatrix degradationMaturationAssemblyArg interacts with cortactin to promote adhesion-dependent cell edge protrusion
Lapetina S, Mader CC, Machida K, Mayer BJ, Koleske AJ. Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion. Journal Of Cell Biology 2009, 185: 503-519. PMID: 19414610, PMCID: PMC2700396, DOI: 10.1083/jcb.200809085.Peer-Reviewed Original ResearchConceptsCell edge protrusionEdge protrusionActin polymerization machineryAdhesion-dependent phosphorylationCell-matrix adhesionPro-rich motifMutation of residuesPolymerization machinerySH2 domainDomain bindsC-terminusCortactinMolecular mechanismsGene kinaseSimilar defectsAdditional binding sitesCatalytic eventsBinding sitesArgInteractsFibroblast adhesionProtrusionNck1KinasePhosphorylation
2007
A Critical Role for Cortactin Phosphorylation by Abl-Family Kinases in PDGF-Induced Dorsal-Wave Formation
Boyle SN, Michaud GA, Schweitzer B, Predki PF, Koleske AJ. A Critical Role for Cortactin Phosphorylation by Abl-Family Kinases in PDGF-Induced Dorsal-Wave Formation. Current Biology 2007, 17: 445-451. PMID: 17306540, DOI: 10.1016/j.cub.2007.01.057.Peer-Reviewed Original ResearchConceptsAbl family kinasesCortactin phosphorylationActin regulatory protein cortactinTyrosine kinaseAbl family tyrosine kinasesSrc family kinasesNonreceptor tyrosine kinaseHuman protein microarrayCell morphogenesisActin reorganizationCytoskeletal rearrangementsProtein cortactinGrowth factor receptorLamellipodial protrusionCytoskeletal structuresCell motilityProper regulationPDGF treatmentTyrosine residuesCortactinKinaseNovel substrateDownstream actionsPhosphorylationProtein microarrays