2024
The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells
Liao X, Li W, Zhou H, Rajendran B, Li A, Ren J, Luan Y, Calderwood D, Turk B, Tang W, Liu Y, Wu D. The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells. Nature Communications 2024, 15: 603. PMID: 38242867, PMCID: PMC10798966, DOI: 10.1038/s41467-024-44885-0.Peer-Reviewed Original ResearchConceptsCD8+ T cellsT cellsCancer immunotherapyMouse CD8+ T cellsAnti-tumor immunityTumor growth inhibition abilityAnti-tumor effectsInhibition of neddylationCD8Effector functionsTCR stimulationIL2 signalingCentral signaling pathwaysCore signaling pathwaysEffector activityNegative regulatory mechanismsTranslational implicationsImmunotherapyGrowth inhibition abilityCytokine signalingTCRProteomic alterationsSignaling pathwayCancerCRISPR-based screens
2022
Organization, dynamics and mechanoregulation of integrin-mediated cell–ECM adhesions
Kanchanawong P, Calderwood DA. Organization, dynamics and mechanoregulation of integrin-mediated cell–ECM adhesions. Nature Reviews Molecular Cell Biology 2022, 24: 142-161. PMID: 36168065, PMCID: PMC9892292, DOI: 10.1038/s41580-022-00531-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionCytoskeletonExtracellular MatrixFocal AdhesionsIntegrinsSignal TransductionTissue AdhesionsConceptsExtracellular matrixCell-ECM adhesionCell-ECM interactionsLocal extracellular matrixAdhesion maturationAdhesion complexesAnimal cellsBiochemical signalingTransmembrane receptorsAdhesion structuresCell shapeIntegrin familyMolecular natureAge-related dysfunctionAdvanced imaging approachesCharacterization of rearrangementsMechanical forcesSignalingTissue formationAdhesionCytoskeletonMechanoregulationImmune responseImaging approachImproved understanding
2020
Signalling through cerebral cavernous malformation protein networks
Su VL, Calderwood DA. Signalling through cerebral cavernous malformation protein networks. Open Biology 2020, 10: 200263. PMID: 33234067, PMCID: PMC7729028, DOI: 10.1098/rsob.200263.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCarrier ProteinsDisease ManagementDisease SusceptibilityGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansIntracellular SpaceMutationProtein BindingProtein Interaction Domains and MotifsProtein Interaction MappingProtein Interaction MapsProtein TransportSignal TransductionConceptsCCM proteinsCerebral cavernous malformationsCell junctionalMEKK3-MEK5Protein complexesAdaptor proteinProtein functionSubcellular localizationCytoskeletal reorganizationComplex proteinsProtein networkRhoA-ROCKMolecular basisProtein activityGene expressionFunction mutationsCell adhesionCell contractilityProteinPathwayLeaky blood vesselsCurrent knowledgeDisease pathologyCdc42Recent advancesChapter 22: Structural and signaling functions of integrins
Kadry YA, Calderwood DA. Chapter 22: Structural and signaling functions of integrins. Biochimica Et Biophysica Acta (BBA) - Biomembranes 2020, 1862: 183206. PMID: 31991120, PMCID: PMC7063833, DOI: 10.1016/j.bbamem.2020.183206.Peer-Reviewed Original ResearchConceptsFunction of integrinsAbility of integrinsTransmembrane adhesion receptorsNon-redundant functionsDifferent integrin heterodimersExtracellular matrix proteinsComplex structural rearrangementsDiverse downstreamCytoskeletal complexMetazoan lifeExtracellular environmentΒ-subunitAdhesion receptorsIntegrin heterodimersIntegrin familyMatrix proteinsCell adhesionIntegrinsStructural rearrangementsHeterodimersRecent advancesSubunitsSignalingProteinFunction
2018
Kindlin-2 interacts with a highly conserved surface of ILK to regulate focal adhesion localization and cell spreading
Kadry YA, Huet-Calderwood C, Simon B, Calderwood DA. Kindlin-2 interacts with a highly conserved surface of ILK to regulate focal adhesion localization and cell spreading. Journal Of Cell Science 2018, 131: jcs221184. PMID: 30254023, PMCID: PMC6215391, DOI: 10.1242/jcs.221184.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell AdhesionFocal AdhesionsHumansMembrane ProteinsNeoplasm ProteinsProtein Serine-Threonine KinasesSignal TransductionConceptsIntegrin-linked kinaseFocal adhesion localizationKindlin-2Cell spreadingIntegrin-mediated signalingILK bindingILK mutantPseudokinase domainIntegrin signalingKnockdown cellsAxis downstreamC-lobeCell morphologyMutantsSignalingCentral rolePKDComplete understandingLocalizationFirst personKinaseAdaptorSitesSpeciesIntegrins
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
2014
Up-regulation of Thrombospondin-2 in Akt1-null Mice Contributes to Compromised Tissue Repair Due to Abnormalities in Fibroblast Function*
Bancroft T, Bouaouina M, Roberts S, Lee M, Calderwood DA, Schwartz M, Simons M, Sessa WC, Kyriakides TR. Up-regulation of Thrombospondin-2 in Akt1-null Mice Contributes to Compromised Tissue Repair Due to Abnormalities in Fibroblast Function*. Journal Of Biological Chemistry 2014, 290: 409-422. PMID: 25389299, PMCID: PMC4281743, DOI: 10.1074/jbc.m114.618421.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementFibroblastsGene Expression RegulationGenetic Complementation TestIntegrin beta1MiceMice, KnockoutNeuropeptidesNitric Oxide Synthase Type IIIPrimary Cell CultureProto-Oncogene Proteins c-aktRac1 GTP-Binding ProteinRNA, Small InterferingSignal TransductionSkinThrombospondinsWound HealingWounds, NonpenetratingDynamin 2 regulation of integrin endocytosis, but not VEGF signaling, is crucial for developmental angiogenesis
Lee MY, Skoura A, Park EJ, Landskroner-Eiger S, Jozsef L, Luciano AK, Murata T, Pasula S, Dong Y, Bouaouina M, Calderwood DA, Ferguson SM, De Camilli P, Sessa WC. Dynamin 2 regulation of integrin endocytosis, but not VEGF signaling, is crucial for developmental angiogenesis. Development 2014, 141: 1465-1472. PMID: 24598168, PMCID: PMC3957370, DOI: 10.1242/dev.104539.Peer-Reviewed Original ResearchConceptsΒ1 integrinFocal adhesion sizeGrowth factor signalingVascular endothelial growth factor signalingEndocytic turnoverIntegrin endocytosisDynamin 2Adhesion sizeFactor signalingDevelopmental angiogenesisAngiogenic sproutingCell migrationCultured endothelial cellsMultiple integrinsInducible lossIntegrinsMorphogenesisActivation stateDNM2Endothelial cellsAngiogenesisVivoEndocytosisSurface levelSignalingIntegrin Cytoplasmic Tail Interactions
Morse EM, Brahme NN, Calderwood DA. Integrin Cytoplasmic Tail Interactions. Biochemistry 2014, 53: 810-820. PMID: 24467163, PMCID: PMC3985435, DOI: 10.1021/bi401596q.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytoplasmCytoskeletonHumansIntegrinsIntracellular Signaling Peptides and ProteinsMechanotransduction, CellularSignal TransductionConceptsIntegrin-interacting proteinsIntegrin cytoplasmic tailsCell surface adhesion receptorsIntegrin-binding proteinsHeterodimeric cell-surface adhesion receptorsSurface adhesion receptorsExtracellular ligandsMulticellular lifeCytoplasmic tailIntegrin engagementCell motilityExtracellular environmentTransduce chemicalIntegrin activityIntegrin localizationIntracellular proteinsAdhesion receptorsTail interactionsMechanical signalsProteinIntegrinsCellsCytoskeletonLocalizationTraffickingCerebral cavernous malformation proteins at a glance
Draheim KM, Fisher OS, Boggon TJ, Calderwood DA. Cerebral cavernous malformation proteins at a glance. Journal Of Cell Science 2014, 127: 701-707. PMID: 24481819, PMCID: PMC3924200, DOI: 10.1242/jcs.138388.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCapillary PermeabilityCarrier ProteinsCentral Nervous System NeoplasmsHemangioma, Cavernous, Central Nervous SystemHumansKRIT1 ProteinMembrane ProteinsMicrotubule-Associated ProteinsNeoplasm ProteinsProto-Oncogene ProteinsRho GTP-Binding ProteinsSignal TransductionConceptsAdaptor proteinCerebral Cavernous Malformation ProteinsMulti-domain adaptor proteinBasic cellular processesProtein-protein interactionsCerebral cavernous malformationsAccompanying posterGlance articleCCM proteinsCellular processesProtein functionCellular phenotypesTrimeric complexFunction mutationsCell adhesionCell scienceProteinLeaky blood vesselsFocal neurological defectsCurrent understandingNeurological defectsCytoskeletalGenesPDCD10KRIT1Differences in binding to the ILK complex determines kindlin isoform adhesion localization and integrin activation
Huet-Calderwood C, Brahme NN, Kumar N, Stiegler AL, Raghavan S, Boggon TJ, Calderwood DA. Differences in binding to the ILK complex determines kindlin isoform adhesion localization and integrin activation. Journal Of Cell Science 2014, 127: 4308-4321. PMID: 25086068, PMCID: PMC4179494, DOI: 10.1242/jcs.155879.Peer-Reviewed Original ResearchConceptsIntegrin activationKindlin-2Kindlin-3Focal adhesion proteinsFunctional differencesIntegrin-linked kinaseILK complexAdhesion proteinsF2 subdomainMolecular basisIsoform specificityComplex bindsKindlinFA targetingActivation defectsCell adhesionActivationFALocalizesKinaseGFPSignalingILKIsoformsProtein
2013
Substrate and Inhibitor Specificity of the Type II p21-Activated Kinase, PAK6
Gao J, Ha BH, Lou HJ, Morse EM, Zhang R, Calderwood DA, Turk BE, Boggon TJ. Substrate and Inhibitor Specificity of the Type II p21-Activated Kinase, PAK6. PLOS ONE 2013, 8: e77818. PMID: 24204982, PMCID: PMC3810134, DOI: 10.1371/journal.pone.0077818.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCatalytic DomainCrystallizationCrystallography, X-RayHEK293 CellsHumansIndolesModels, MolecularMolecular Sequence DataP21-Activated KinasesPeptide FragmentsPhosphorylationProtein ConformationPyrazolesPyrrolesSequence Homology, Amino AcidSignal TransductionSubstrate SpecificitySunitinibConceptsP21-activated kinaseCo-crystal structureRho family small GTPasesPeptide substrate specificityATP-competitive inhibitorsStructure-function relationshipsSmall GTPasesPAK familyCatalytic domainMelanoma-associated mutationsSubstrate specificityInhibitor specificityPAK6Receptor signalingPF-3758309Important effectorsMechanism 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
Structural Basis for Small G Protein Effector Interaction of Ras-related Protein 1 (Rap1) and Adaptor Protein Krev Interaction Trapped 1 (KRIT1)
Li X, Zhang R, Draheim KM, Liu W, Calderwood DA, Boggon TJ. Structural Basis for Small G Protein Effector Interaction of Ras-related Protein 1 (Rap1) and Adaptor Protein Krev Interaction Trapped 1 (KRIT1). Journal Of Biological Chemistry 2012, 287: 22317-22327. PMID: 22577140, PMCID: PMC3381192, DOI: 10.1074/jbc.m112.361295.Peer-Reviewed Original ResearchAmino Acid SequenceCrystallography, X-RayGene Expression RegulationGTP PhosphohydrolasesHemangioma, Cavernous, Central Nervous SystemHumansIntegrinsKRIT1 ProteinMicrotubule-Associated ProteinsModels, BiologicalModels, MolecularMolecular Sequence DataMutagenesisPoint MutationProtein ConformationProtein Interaction MappingProtein Structure, TertiaryProto-Oncogene ProteinsRap1 GTP-Binding ProteinsSequence Homology, Amino AcidSignal TransductionFilamins in Mechanosensing and Signaling
Razinia Z, Mäkelä T, Ylänne J, Calderwood DA. Filamins in Mechanosensing and Signaling. Annual Review Of Biophysics 2012, 41: 227-246. PMID: 22404683, PMCID: PMC5508560, DOI: 10.1146/annurev-biophys-050511-102252.Peer-Reviewed Original ResearchConceptsPlasma membraneActin filamentsActin-binding proteinsExtracellular matrix connectionsCortical rigidityActin cytoskeletonCellular functionsCell cortexTranscription factorsTransmembrane receptorsAdhesion proteinsCell shapeFilaminIon channelsDiverse arrayFunctional evidenceEssential roleProteinMatrix connectionsPhysical forcesMembraneFilamentsCytoskeletalMechanosensingCytoskeleton
2011
Talin and Signaling Through Integrins
Bouaouina M, Harburger DS, Calderwood DA. Talin and Signaling Through Integrins. Methods In Molecular Biology 2011, 757: 325-347. PMID: 21909921, PMCID: PMC5642996, DOI: 10.1007/978-1-61779-166-6_20.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological AssayCHO CellsCricetinaeFlow CytometryIntegrinsProtein BindingRecombinant ProteinsSignal TransductionTalinConceptsCytoplasmic tailIntegrin activationIntegrin β tailsAbility of integrinsIntegrin cytoplasmic tailsShort cytoplasmic tailIntegrin adhesion receptorsBinding of talinDominant-negative constructMulticellular animalsActin cytoskeletonΒ tailExtracellular ligandsTalin domainTalinCharacterization of interactionsIntracellular signalsAdhesion receptorsCell adhesionIntegrin receptorsCultured cellsExtracellular matrixNegative constructsIntegrin subunitsIntegrinsKindlins
Bouaouina M, Calderwood DA. Kindlins. Current Biology 2011, 21: r99-r101. PMID: 21300280, DOI: 10.1016/j.cub.2010.12.002.Peer-Reviewed Original Research
2009
Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase
Chiswell BP, Stiegler AL, Razinia Z, Nalibotski E, Boggon TJ, Calderwood DA. Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase. Journal Of Structural Biology 2009, 170: 157-163. PMID: 19963065, PMCID: PMC2841223, DOI: 10.1016/j.jsb.2009.12.002.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnkyrin RepeatBinding, CompetitiveCrystallizationDNA-Binding ProteinsGene Expression RegulationLIM Domain ProteinsMembrane ProteinsModels, MolecularMolecular Sequence DataMutagenesisProtein BindingProtein Serine-Threonine KinasesSignal TransductionConceptsIntegrin-linked kinaseAnkyrin repeat domainLIM1 domainIPP complexIsoform-specific functionsIntegrin adhesion receptorsDifferent cellular responsesPINCH2Repeat domainPINCH1Point mutagenesisStructural basisAdhesion receptorsCellular responsesAlters localizationDifferential regulationSame binding siteDirect competitionBinding sitesKinaseDomainAnkyrinParvinMutagenesisMammals
2008
Integrin signalling at a glance
Harburger DS, Calderwood DA. Integrin signalling at a glance. Journal Of Cell Science 2008, 122: 159-163. PMID: 19118207, PMCID: PMC2714413, DOI: 10.1242/jcs.018093.Peer-Reviewed Original Research
2007
The N-terminal Domains of Talin Cooperate with the Phosphotyrosine Binding-like Domain to Activate β1 and β3 Integrins*
Bouaouina M, Lad Y, Calderwood DA. The N-terminal Domains of Talin Cooperate with the Phosphotyrosine Binding-like Domain to Activate β1 and β3 Integrins*. Journal Of Biological Chemistry 2007, 283: 6118-6125. PMID: 18165225, DOI: 10.1074/jbc.m709527200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionCytoskeletal ProteinsIntegrin beta1Integrin beta3MiceProtein Structure, TertiarySignal TransductionTalin