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 resolutionPaxillin
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 scatteringRegion
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 effectsBindingLysozyme 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
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