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 ResearchConceptsIntegrin-linked kinaseFocal adhesion localizationKindlin-2Cell spreadingIntegrin-mediated signalingILK bindingILK mutantPseudokinase domainIntegrin signalingKnockdown cellsAxis downstreamC-lobeCell morphologyMutantsSignalingCentral rolePKDComplete understandingLocalizationFirst personKinaseAdaptorSitesSpeciesIntegrins
2016
Nuclear Localization of Integrin Cytoplasmic Domain-associated Protein-1 (ICAP1) Influences β1 Integrin Activation and Recruits Krev/Interaction Trapped-1 (KRIT1) to the Nucleus*
Draheim KM, Huet-Calderwood C, Simon B, Calderwood DA. Nuclear Localization of Integrin Cytoplasmic Domain-associated Protein-1 (ICAP1) Influences β1 Integrin Activation and Recruits Krev/Interaction Trapped-1 (KRIT1) to the Nucleus*. Journal Of Biological Chemistry 2016, 292: 1884-1898. PMID: 28003363, PMCID: PMC5290960, DOI: 10.1074/jbc.m116.762393.Peer-Reviewed Original Research
2015
The Rap1-RIAM pathway prefers β2 integrins
Calderwood DA. The Rap1-RIAM pathway prefers β2 integrins. Blood 2015, 126: 2658-2659. PMID: 26679542, PMCID: PMC4683328, DOI: 10.1182/blood-2015-09-668962.Peer-Reviewed Original ResearchCCM2–CCM3 interaction stabilizes their protein expression and permits endothelial network formation
Draheim KM, Li X, Zhang R, Fisher OS, Villari G, Boggon TJ, Calderwood DA. CCM2–CCM3 interaction stabilizes their protein expression and permits endothelial network formation. Journal Of Cell Biology 2015, 208: 987-1001. PMID: 25825518, PMCID: PMC4384732, DOI: 10.1083/jcb.201407129.Peer-Reviewed Original ResearchMeSH KeywordsApoptosis Regulatory ProteinsBinding SitesCarrier ProteinsCell LineCell ProliferationCentral Nervous SystemCrystallography, X-RayGene ExpressionHemangioma, Cavernous, Central Nervous SystemHumansMembrane ProteinsMutagenesisNeovascularization, PhysiologicPaxillinProtein BindingProtein Interaction MappingProtein Structure, TertiaryProteolysisProto-Oncogene ProteinsRNA InterferenceRNA, Small InterferingSequence AlignmentConceptsBinding-deficient mutantStructure-guided mutagenesisNormal cell growthCerebral cavernous malformationsEndothelial network formationHomology domainCCM3 proteinsProteasomal degradationEndothelial cell network formationMolecular basisCell network formationEssential adaptorCell growthFunctional significanceCCM3 expressionX-ray crystallographyProtein expressionCCM2CCM3Network formationExpressionMutantsHP1MutagenesisAdaptor
2014
Differences 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 adhesionActivationFALocalizesKinaseGFPSignalingILKIsoformsProteinCerebral 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 defectsCytoskeletalGenesPDCD10KRIT1
2013
Kindlin Binds Migfilin Tandem LIM Domains and Regulates Migfilin Focal Adhesion Localization and Recruitment Dynamics*
Brahme NN, Harburger DS, Kemp-O'Brien K, Stewart R, Raghavan S, Parsons M, Calderwood DA. Kindlin Binds Migfilin Tandem LIM Domains and Regulates Migfilin Focal Adhesion Localization and Recruitment Dynamics*. Journal Of Biological Chemistry 2013, 288: 35604-35616. PMID: 24165133, PMCID: PMC3853305, DOI: 10.1074/jbc.m113.483016.Peer-Reviewed Original ResearchConceptsFocal adhesionsLIM domainsActin cytoskeletonFluorescence resonance energy transferFA localizationActin-rich stress fibersC-terminal LIM domainsLIM domain regionTandem LIM domainsTwo-hybrid screenDomain-containing adaptor proteinFocal adhesion localizationIntegrin-binding proteinsIntegrin adhesion receptorsPulldown assaysAdaptor proteinMigfilinFA formationKindlinRecruitment dynamicsStress fibersKindlin-2Integrin activationIntracellular proteinsAdhesion receptorsTalins and kindlins: partners in integrin-mediated adhesion
Calderwood DA, Campbell ID, Critchley DR. Talins and kindlins: partners in integrin-mediated adhesion. Nature Reviews Molecular Cell Biology 2013, 14: 503-517. PMID: 23860236, PMCID: PMC4116690, DOI: 10.1038/nrm3624.Peer-Reviewed Original ResearchConceptsIntegrin activationAdhesion complexesTalin headAmino-terminal headTalin-vinculin interactionsIntegrin cytoplasmic domainIntegrin activation pathwaysIntegrin extracellular domainIntegrin subunitsShort cytoplasmic tailDefective integrin activationPost-translational modificationsFull-length talinTalin-integrin interactionActin-binding siteImportant control pointTransmit chemicalTalin autoinhibitionDisease-causing mutationsKey PointsIntegrinsActin cytoskeletonProtein talinExtracellular ligandsFocal adhesionsIntegrin tailsPurification and SAXS Analysis of the Integrin Linked Kinase, PINCH, Parvin (IPP) Heterotrimeric Complex
Stiegler AL, Grant TD, Luft JR, Calderwood DA, Snell EH, Boggon TJ. Purification and SAXS Analysis of the Integrin Linked Kinase, PINCH, Parvin (IPP) Heterotrimeric Complex. PLOS ONE 2013, 8: e55591. PMID: 23383235, PMCID: PMC3561323, DOI: 10.1371/journal.pone.0055591.Peer-Reviewed Original ResearchConceptsIPP complexEnsemble optimization methodDetailed purification protocolHeterotrimeric protein complexIntegrin Linked KinaseIntegrin adhesion receptorsInter-domain linkerInter-domain interactionsInter-domain contactsGel filtration analysisΑ-parvinLIM1 domainHuman ILKSmall-angle X-ray scatteringHeterotrimeric complexProtein complexesFocal adhesionsAdhesion receptorsPINCH proteinFirst structural characterizationFiltration analysisPurification protocolConformational restraintsKinaseILKMechanism 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
A Conserved Lipid-binding Loop in the Kindlin FERM F1 Domain Is Required for Kindlin-mediated αIIbβ3 Integrin Coactivation*
Bouaouina M, Goult BT, Huet-Calderwood C, Bate N, Brahme NN, Barsukov IL, Critchley DR, Calderwood DA. A Conserved Lipid-binding Loop in the Kindlin FERM F1 Domain Is Required for Kindlin-mediated αIIbβ3 Integrin Coactivation*. Journal Of Biological Chemistry 2012, 287: 6979-6990. PMID: 22235127, PMCID: PMC3293583, DOI: 10.1074/jbc.m111.330845.Peer-Reviewed Original ResearchConceptsIntegrin β tailsTalin FERM domainFERM domainFocal adhesionsΒ tailTalin headHeterodimeric integrin adhesion receptorsIntegrin activationKindlin-1Membrane-binding motifFERM domain proteinsIntegrin β subunitsShort cytoplasmic tailAcidic membrane phospholipidsIntegrin adhesion receptorsΑIIbβ3 integrin activationDomain proteinsIntegrin tailsCytoplasmic domainCytoplasmic tailKindlinKindlin familyDomain interactionsPhospholipid head groupsPolylysine motifFunctional differences between kindlin-1 and kindlin-2 in keratinocytes
Bandyopadhyay A, Rothschild G, Kim S, Calderwood DA, Raghavan S. Functional differences between kindlin-1 and kindlin-2 in keratinocytes. Journal Of Cell Science 2012, 125: 2172-2184. PMID: 22328497, PMCID: PMC3367939, DOI: 10.1242/jcs.096214.Peer-Reviewed Original ResearchConceptsFocal adhesionsKindlin-2Kindlin-1Cell spreadingPeripheral focal adhesionsIntegrin β1Wild-type cellsUnexpected functional consequencesIntegrin β6Wild-type keratinocytesCytoplasmic tailNull keratinocytesKindlinNull cellsFunctional consequencesDirect interactionFunctional differencesUnique functionRelated integrinsIntegrinsCellsAdhesionKeratinocytesIntegrin αvβ6Knockdown
2011
Kindlins
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 sitesKinaseDomainAnkyrinParvinMutagenesisMammalsThe Structure of the N-Terminus of Kindlin-1: A Domain Important for αIIbβ3 Integrin Activation
Goult BT, Bouaouina M, Harburger DS, Bate N, Patel B, Anthis NJ, Campbell ID, Calderwood DA, Barsukov IL, Roberts GC, Critchley DR. The Structure of the N-Terminus of Kindlin-1: A Domain Important for αIIbβ3 Integrin Activation. Journal Of Molecular Biology 2009, 394: 944-956. PMID: 19804783, PMCID: PMC2963925, DOI: 10.1016/j.jmb.2009.09.061.Peer-Reviewed Original ResearchKindlin-1 and -2 Directly Bind the C-terminal Region of β Integrin Cytoplasmic Tails and Exert Integrin-specific Activation Effects*
Harburger DS, Bouaouina M, Calderwood DA. Kindlin-1 and -2 Directly Bind the C-terminal Region of β Integrin Cytoplasmic Tails and Exert Integrin-specific Activation Effects*. Journal Of Biological Chemistry 2009, 284: 11485-11497. PMID: 19240021, PMCID: PMC2670154, DOI: 10.1074/jbc.m809233200.Peer-Reviewed Original Research
2008
The structural basis of integrin-linked kinase–PINCH interactions
Chiswell BP, Zhang R, Murphy JW, Boggon TJ, Calderwood DA. The structural basis of integrin-linked kinase–PINCH interactions. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 20677-20682. PMID: 19074270, PMCID: PMC2634877, DOI: 10.1073/pnas.0811415106.Peer-Reviewed Original ResearchConceptsIntegrin-linked kinaseLIM1 domainGrowth factor signalingAtomic resolution descriptionILK bindingAnkyrin repeatsILK-PINCHHeterotrimeric complexZinc fingerMolecular basisMutagenesis dataStructural basisCell adhesionPoint mutationsConformational flexibilityKey interactionsParvinConvergence pointLim1DomainAnkyrinKinaseComplexesRepeatsSignaling
2003
The Kindler Syndrome Protein Is Regulated by Transforming Growth Factor-β and Involved in Integrin-mediated Adhesion*
Kloeker S, Major MB, Calderwood DA, Ginsberg MH, Jones DA, Beckerle MC. The Kindler Syndrome Protein Is Regulated by Transforming Growth Factor-β and Involved in Integrin-mediated Adhesion*. Journal Of Biological Chemistry 2003, 279: 6824-6833. PMID: 14634021, DOI: 10.1074/jbc.m307978200.Peer-Reviewed Original ResearchMeSH KeywordsActinsAmino Acid SequenceBlotting, NorthernBlotting, WesternCell AdhesionCell LineCell MovementCytoplasmCytoskeletonDisease ProgressionDNA, ComplementaryExtracellular Matrix ProteinsFluorescent Antibody Technique, IndirectGene Expression RegulationHumansIntegrin beta1Integrin beta3IntegrinsMembrane ProteinsModels, MolecularMolecular Sequence DataMutationNeoplasm ProteinsOligonucleotide Array Sequence AnalysisProtein BindingProtein Structure, TertiaryRNARNA, MessengerRNA, Small InterferingSequence Homology, Amino AcidTime FactorsTransfectionTransforming Growth Factor betaUp-RegulationConceptsHuman mammary epithelial cellsCytoplasmic domainIntegrin cytoplasmic domainBeta3 integrin cytoplasmic domainsCDNA microarray analysisTGF-beta stimulationNormal cell spreadingMammary epithelial cellsSyndrome proteinFERM domainFocal adhesionsTranscriptional profilesProtein abundanceCritical residuesMicroarray analysisCell spreadingGene leadTalin-FERMCell migrationCancer progressionIntegrin betaGenesCell processesAutosomal recessive genodermatosisEpithelial cells