2021
PPP6C negatively regulates oncogenic ERK signaling through dephosphorylation of MEK
Cho E, Lou HJ, Kuruvilla L, Calderwood DA, Turk BE. PPP6C negatively regulates oncogenic ERK signaling through dephosphorylation of MEK. Cell Reports 2021, 34: 108928. PMID: 33789117, PMCID: PMC8068315, DOI: 10.1016/j.celrep.2021.108928.Peer-Reviewed Original ResearchConceptsProtein kinase cascadeCore oncogenic pathwaysKey negative regulatorOncogenic ERKERK pathway activationCrosstalk regulationCentral kinaseKinase cascadePhosphorylation sitesRegulatory subunitRaf-MEKNegative regulatorERK pathwayDrug targetsOncogenic pathwaysMEKMEK inhibitorsDephosphorylationPathway activationPPP6CPhosphatasePathwayERKHyperphosphorylationCascade
2019
The subcellular localization of type I p21-activated kinases is controlled by the disordered variable region and polybasic sequences
Sun X, Su VL, Calderwood DA. The subcellular localization of type I p21-activated kinases is controlled by the disordered variable region and polybasic sequences. Journal Of Biological Chemistry 2019, 294: 14319-14332. PMID: 31391252, PMCID: PMC6768646, DOI: 10.1074/jbc.ra119.007692.Peer-Reviewed Original ResearchConceptsCell-cell contactCell-cell junctionsPolybasic sequenceP21-activated kinaseSmall GTPases RacVariable regionsCell-cell boundariesPAK regulationDomain organizationCdc42 bindingAdhesion dynamicsCRIB domainGTPases RacSubcellular localizationTruncation mutantsKinase domainKinase effectorsCellular signalsExtensive similaritySequence regionsPAK1Cell adhesionCdc42PAKKinase
2016
Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-β–dependent mechanisms
Shi X, Mihaylova VT, Kuruvilla L, Chen F, Viviano S, Baldassarre M, Sperandio D, Martinez R, Yue P, Bates JG, Breckenridge DG, Schlessinger J, Turk BE, Calderwood DA. Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-β–dependent mechanisms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e4558-e4566. PMID: 27432991, PMCID: PMC4978292, DOI: 10.1073/pnas.1608319113.Peer-Reviewed Original ResearchMeSH KeywordsAzepinesCell Line, TumorCell ProliferationColorectal NeoplasmsDrug ResistanceGene Expression Regulation, NeoplasticHCT116 CellsHEK293 CellsHumansMolecular StructureProteinsProto-Oncogene Proteins c-mycReceptors, Transforming Growth Factor betaRNA InterferenceSignal TransductionTranscription FactorsTransforming Growth Factor betaTriazolesConceptsTGF-β receptor activityExtraterminal domain protein inhibitorsRegulation of MYCCancer cellsBET bromodomain inhibitionShRNA screeningProtein 33TGF-β receptor expressionBromodomain inhibitorsProtein inhibitorInhibition of TGFColorectal cancer cellsBromodomain inhibitionBETi resistanceCancer therapeuticsNew therapeutic benefitsDurable responsesMYCDependent mechanismReceptor expressionTherapeutic benefitBETiReceptor activityResistant stateAntiproliferative effects
2015
PAK6 targets to cell–cell adhesions through its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape
Morse EM, Sun X, Olberding JR, Ha BH, Boggon TJ, Calderwood DA. PAK6 targets to cell–cell adhesions through its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape. Journal Of Cell Science 2015, 129: 380-393. PMID: 26598554, PMCID: PMC4732285, DOI: 10.1242/jcs.177493.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, CDCadherinsCdc42 GTP-Binding ProteinCell AdhesionCell Line, TumorEpithelial CellsHEK293 CellsHumansIntercellular JunctionsMolecular Sequence DataP21-Activated KinasesProtein BindingProtein Interaction Domains and MotifsProtein Sorting SignalsProtein TransportConceptsCell-cell adhesionN-terminusCdc42/Rac interactive binding (CRIB) domainSerine/threonine kinaseP21-activated kinase (PAK) familyCdc42-dependent mannerPolybasic regionThreonine kinaseCdc42 knockdownKinase familyBinding domainsKinase activityImportant regulatorCell adhesionPAK6Broader rolePAKAdhesionTargetingCdc42PAK1KinaseKnockdownRegulatorMutations
2013
Mechanism for KRIT1 Release of ICAP1-Mediated Suppression of Integrin Activation
Liu W, Draheim KM, Zhang R, Calderwood DA, Boggon TJ. Mechanism for KRIT1 Release of ICAP1-Mediated Suppression of Integrin Activation. Molecular Cell 2013, 49: 719-729. PMID: 23317506, PMCID: PMC3684052, DOI: 10.1016/j.molcel.2012.12.005.Peer-Reviewed Original ResearchAdaptor Proteins, Signal TransducingAmino Acid MotifsAmino Acid SequenceCell Line, TumorConserved SequenceCrystallography, X-RayHumansHydrogen BondingHydrophobic and Hydrophilic InteractionsIntegrin beta1Intracellular Signaling Peptides and ProteinsKRIT1 ProteinMembrane ProteinsMicrotubule-Associated ProteinsModels, MolecularMolecular Sequence DataProtein BindingProtein Interaction Domains and MotifsProtein Structure, QuaternaryProto-Oncogene ProteinsSignal Transduction
2012
Filamin A controls matrix metalloproteinase activity and regulates cell invasion in human fibrosarcoma cells
Baldassarre M, Razinia Z, Brahme NN, Buccione R, Calderwood DA. Filamin A controls matrix metalloproteinase activity and regulates cell invasion in human fibrosarcoma cells. Journal Of Cell Science 2012, 125: 3858-3869. PMID: 22595522, PMCID: PMC3462082, DOI: 10.1242/jcs.104018.Peer-Reviewed Original ResearchMeSH KeywordsActinsCell AdhesionCell Line, TumorCell MovementContractile ProteinsEnzyme ActivationExtracellular MatrixFibrosarcomaFilaminsGene Knockdown TechniquesHumansIntegrinsMatrix Metalloproteinase 14Matrix Metalloproteinase 2Microfilament ProteinsNeoplasm InvasivenessPhenotypeProtein Structure, TertiaryConceptsFilamin AActin cytoskeletonCell invasionActin-binding domainCell surface adhesion proteinsControls cell motilityActin-binding proteinsIntegrin adhesion receptorsRandom cell migrationAbility of cellsArray of intracellularBreast cancer lossSurface adhesion proteinsHuman fibrosarcoma cellsExtracellular matrix degradationMatrix metalloproteinase activityFilamin expressionKnockdown cellsAdhesion proteinsCell motilityMetalloproteinase activityActin filamentsAdhesion receptorsFilaminECM remodeling
2011
The E3 ubiquitin ligase specificity subunit ASB2α targets filamins for proteasomal degradation by interacting with the filamin actin-binding domain
Razinia Z, Baldassarre M, Bouaouina M, Lamsoul I, Lutz PG, Calderwood DA. The E3 ubiquitin ligase specificity subunit ASB2α targets filamins for proteasomal degradation by interacting with the filamin actin-binding domain. Journal Of Cell Science 2011, 124: 2631-2641. PMID: 21750192, PMCID: PMC3138704, DOI: 10.1242/jcs.084343.Peer-Reviewed Original ResearchConceptsFilamin degradationProteasomal degradationCell differentiationDomain of filaminActin-rich structuresUbiquitin-proteasome pathwayExtracellular matrix connectionsActin cytoskeletonTransmembrane proteinSubcellular localizationMolecular basisSignaling cascadesASB2αActin filamentsFilaminAcute degradationBiochemical assaysMyeloid leukemia cellsImportant familyActinEarly eventsProteinLeukemia cellsImportant mechanismDifferentiation
2009
Filamins Regulate Cell Spreading and Initiation of Cell Migration
Baldassarre M, Razinia Z, Burande CF, Lamsoul I, Lutz PG, Calderwood DA. Filamins Regulate Cell Spreading and Initiation of Cell Migration. PLOS ONE 2009, 4: e7830. PMID: 19915675, PMCID: PMC2773003, DOI: 10.1371/journal.pone.0007830.Peer-Reviewed Original ResearchConceptsCell spreadingLarge actin-binding proteinCell biological analysesCell migrationActin-binding proteinsLoss of FlnAShRNA-mediated knockdownInitiation of migrationInhibition of initiationRecent knockout studiesProteasomal degradationKnockdown cellsInitiation of motilityKnockout studiesFilaminSingle knockoutImpairs migrationFLNAFLNBBiological analysisKnockdownProteinObserved defectsCellsPeriventricular heterotopiaFilamin A–β1 Integrin Complex Tunes Epithelial Cell Response to Matrix Tension
Gehler S, Baldassarre M, Lad Y, Leight JL, Wozniak MA, Riching KM, Eliceiri KW, Weaver VM, Calderwood DA, Keely PJ. Filamin A–β1 Integrin Complex Tunes Epithelial Cell Response to Matrix Tension. Molecular Biology Of The Cell 2009, 20: 3224-3238. PMID: 19458194, PMCID: PMC2710838, DOI: 10.1091/mbc.e08-12-1186.Peer-Reviewed Original ResearchConceptsFilamin AExtracellular matrixProtein filamin AHigh-density gelsMatrix tensionCollagen gelsMechanosensitive complexBreast epithelial cellsCellular contractilityMatrix stiffnessMorphogenesisEpithelial cell responsesCell typesDuctal morphogenesisEpithelial cellsCellsCollagen matrixGel contractionActinCollagen remodelingIntegrinsCell responsesCollagen fibrilsRemodelingGel
2008
ASB2 targets filamins A and B to proteasomal degradation
Heuzé ML, Lamsoul I, Baldassarre M, Lad Y, Lévêque S, Razinia Z, Moog-Lutz C, Calderwood DA, Lutz PG. ASB2 targets filamins A and B to proteasomal degradation. Blood 2008, 112: 5130-5140. PMID: 18799729, PMCID: PMC2597609, DOI: 10.1182/blood-2007-12-128744.Peer-Reviewed Original ResearchConceptsAnkyrin repeat-containing proteinFilamin AE3 ubiquitin ligase complexActin-binding protein filamin AFilamin degradationRepeat-containing proteinUbiquitin ligase complexSeries of proliferationHematopoietic cell differentiationProtein filamin AAcid-induced differentiationSuppressor of cytokineLigase complexSpecificity subunitLeukemia cellsHematopoietic differentiationHematopoietic progenitor cellsProteasomal degradationMolecular basisAcute promyelocytic leukemia cellsSpecific proteinsCell spreadingPromyelocytic leukemia cellsArrest of differentiationCell differentiation