2022
Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4)
Ha B, Yigit S, Natarajan N, Morse E, Calderwood D, Boggon T. Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4). Communications Biology 2022, 5: 1257. PMID: 36385162, PMCID: PMC9669019, DOI: 10.1038/s42003-022-04157-3.Peer-Reviewed Original ResearchConceptsP21-activated kinase 4Integrin adhesion receptorsMolecular basisAdhesion receptorsIntegrin β5Potential cellular rolesIntegrin β tailsKinase 4Membrane-proximal halfSubstrate-binding grooveSubstrate-binding siteSite-directed mutagenesisCellular rolesPhosphoacceptor sitesΒ tailExtracellular ligandsCytoplasmic signalingCytoplasmic tailKinase domainMultiple kinasesIntegrin complexΒ5 integrinsΒ5TailMutagenesis
2020
Serine phosphorylation of the small phosphoprotein ICAP1 inhibits its nuclear accumulation
Su VL, Simon B, Draheim KM, Calderwood DA. Serine phosphorylation of the small phosphoprotein ICAP1 inhibits its nuclear accumulation. Journal Of Biological Chemistry 2020, 295: 3269-3284. PMID: 32005669, PMCID: PMC7062153, DOI: 10.1074/jbc.ra119.009794.Peer-Reviewed Original ResearchConceptsIntegrin cytoplasmic domain-associated protein-1N-terminal regionNuclear accumulationP21-activated kinase 4Ser-10Nuclear roleSerine phosphorylationNuclear localizationPhosphorylation-mimicking substitutionsNuclear localization signalCell-cell junctionsSer-25Localization signalKRIT1 functionThreonine residuesAdaptor proteinKRIT1 lossSubcellular localizationNeurovascular dysplasiaBlood vessel integrityVascular developmentKinase 4Cultured cellsPhosphorylationProtein 1
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
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
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 effectors