2019
Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy
Brodehl A, Rezazadeh S, Williams T, Munsie NM, Liedtke D, Oh T, Ferrier R, Shen Y, Jones SJM, Stiegler AL, Boggon TJ, Duff HJ, Friedman JM, Gibson WT, Consortium F, Childs SJ, Gerull B. Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy. Translational Research 2019, 208: 15-29. PMID: 30802431, PMCID: PMC7412573, DOI: 10.1016/j.trsl.2019.02.004.Peer-Reviewed Original ResearchConceptsIntegrin-linked kinase geneFirst LIM domainIntegrin-linked kinaseLIM domainsActin cytoskeletonRat myoblast cellsZebrafish showKinase geneCytoplasmic localizationDisease genesArrhythmogenic cardiomyopathyLife-threatening ventricular arrhythmiasMyoblast cellsJunctional proteinsHuman variantsILKSudden cardiac deathGenesFibro-fatty replacementNormal cardiac functionHalf of casesFunctional evidenceHeart muscle disorderMissense variantsDe novo
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 adhesionActivationFALocalizesKinaseGFPSignalingILKIsoformsProtein
2013
Purification 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 restraintsKinaseILK
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