2017
Phosphorylated 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
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
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 interactionsInvasionCellsPhosphotyrosineSitesRegulation of Actin Polymerization and Adhesion-Dependent Cell Edge Protrusion by the Abl-Related Gene (Arg) Tyrosine Kinase and N-WASp
Miller MM, Lapetina S, MacGrath SM, Sfakianos MK, Pollard TD, Koleske AJ. Regulation of Actin Polymerization and Adhesion-Dependent Cell Edge Protrusion by the Abl-Related Gene (Arg) Tyrosine Kinase and N-WASp. Biochemistry 2010, 49: 2227-2234. PMID: 20146487, PMCID: PMC2836179, DOI: 10.1021/bi901721u.Peer-Reviewed Original ResearchConceptsCell edge protrusionN-WASPActin polymerizationEdge protrusionN-WASP-dependent actin polymerizationGene Tyrosine KinaseFluorescent protein fusionsNovel binding partnerExtracellular cuesProtein fusionsSH2 domainExtracellular stimuliActin cytoskeletonSH3 domainBinding partnerCellular protrusionsPoint mutantsAffinity purificationTyrosine kinasePhysical interactionSH3PhosphorylationArgABLPotential link
2009
Regulation of cell migration and morphogenesis by Abl-family kinases: emerging mechanisms and physiological contexts
Bradley WD, Koleske AJ. Regulation of cell migration and morphogenesis by Abl-family kinases: emerging mechanisms and physiological contexts. Journal Of Cell Science 2009, 122: 3441-3454. PMID: 19759284, PMCID: PMC2746129, DOI: 10.1242/jcs.039859.Peer-Reviewed Original ResearchConceptsAbl family kinasesNon-receptor tyrosine kinaseWAVE family proteinsCell-specific proteinsActivation of cortactinExtracellular cuesEpithelial morphogenesisAdhesion dynamicsCytoskeletal rearrangementsEssential regulatorPhysiological contextCell motilityActin polymerizationCytoskeletal changesPhysiological processesTyrosine kinaseGenetic studiesKinaseMorphogenesisCell contractilityCell migrationProteinComplex processImmune systemCytoskeletonCortactin 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 degradationMaturationAssembly
2008
The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse
Huang Y, Comiskey EO, Dupree RS, Li S, Koleske AJ, Burkhardt JK. The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse. Blood 2008, 112: 111-119. PMID: 18305217, PMCID: PMC2435682, DOI: 10.1182/blood-2007-10-118232.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAnimalsCells, CulturedHumansInterleukin-2Jurkat CellsLymphocyte ActivationMiceMice, KnockoutPhosphorylationProtein BindingProteinsProto-Oncogene Proteins c-ablPseudopodiaReceptors, Antigen, T-CellSignal TransductionT-LymphocytesTranscription, GeneticWiskott-Aldrich Syndrome Protein FamilyConceptsC-AblImmune synapseActin responseC-Abl nonreceptor tyrosine kinaseT cell activationTyrosine kinaseC-Abl tyrosine kinaseC-Abl bindsActin regulatory proteinsNonreceptor tyrosine kinaseChemokine-induced T cell migrationT cell receptor engagementSH2 domainActin dynamicsActin reorganizationTyrosine phosphorylationRegulatory proteinsActin polymerizationDownstream eventsNormal localizationConditional knockout miceCoordinate actionReceptor engagementKinaseLamellipodial spreading
2007
The Abl-related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin
Peacock JG, Miller AL, Bradley WD, Rodriguez OC, Webb DJ, Koleske AJ. The Abl-related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin. Molecular Biology Of The Cell 2007, 18: 3860-3872. PMID: 17652459, PMCID: PMC1995720, DOI: 10.1091/mbc.e07-01-0075.Peer-Reviewed Original ResearchConceptsFocal adhesion dynamicsFocal adhesionsActomyosin contractilityAdhesion dynamicsActin-dependent protrusionsGene Tyrosine KinaseCell migrationCell body translocationAbl family kinasesWild-type cellsC-terminal halfDistinct functional domainsN-terminal halfF-actin stress fibersStress fiber formationInhibits cell migrationKinase inhibitsFamily kinasesCell peripheryStress fibersActin polymerizationFunctional domainsKinase activityTyrosine kinaseWT cells