2017
Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation
Karabadzhak AG, Petti LM, Barrera FN, Edwards APB, Moya-Rodríguez A, Polikanov YS, Freites JA, Tobias DJ, Engelman DM, DiMaio D. Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e7262-e7271. PMID: 28808001, PMCID: PMC5584431, DOI: 10.1073/pnas.1705622114.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCattleCell LineCell Transformation, ViralDimerizationHumansMembrane ProteinsMiceMolecular ConformationOncogene Proteins, ViralPapillomaviridaePapillomavirus InfectionsProtein MultimerizationReceptor, Platelet-Derived Growth Factor betaConceptsTransmembrane domainE5 proteinE5 dimerPlatelet-derived growth factor β receptorGrowth factor β receptorActive dimeric conformationPDGF β-receptorTransmembrane dimerProtein bindsMembrane environmentReceptor dimerizationDimeric conformationAtom molecular dynamics simulationsBiochemical experimentsMouse cellsMolecular mechanismsActive dimerΒ receptorBovine papillomavirusProteinSpecific interactionsMembrane modelingReceptor activationDimerizationComplexes
2001
Mechanisms of cell transformation by papillomavirus E5 proteins
DiMaio D, Mattoon D. Mechanisms of cell transformation by papillomavirus E5 proteins. Oncogene 2001, 20: 7866-7873. PMID: 11753669, DOI: 10.1038/sj.onc.1204915.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBovine papillomavirus 1Cell Transformation, ViralErbB ReceptorsOncogene Proteins, ViralReceptor, Platelet-Derived Growth Factor betaVacuolar Proton-Translocating ATPasesConceptsE5 proteinBovine papillomavirus E5 proteinCellular signal transduction pathwaysSignal transduction pathwaysLigand-independent fashionGrowth factor receptor activityReceptor tyrosine kinasesTransforming proteinTransduction pathwaysGrowth factor receptorVacuolar ATPaseReceptor dimerizationTyrosine kinaseCell transformationProteinViral transformationBovine papillomavirusFactor receptorUnique mechanismStable complexesNew insightsReceptor activityPathwayReceptorsKinaseIdentification of the transmembrane dimer interface of the bovine papillomavirus E5 protein
Mattoon D, Gupta K, Doyon J, Loll P, DiMaio D. Identification of the transmembrane dimer interface of the bovine papillomavirus E5 protein. Oncogene 2001, 20: 3824-3834. PMID: 11439346, DOI: 10.1038/sj.onc.1204523.Peer-Reviewed Original ResearchConceptsBovine papillomavirus E5 proteinE5 proteinDimer interfacePlatelet-derived growth factor β receptorEssential glutamine residueHeterologous dimerization domainGrowth factor β receptorNon-productive interactionsReceptor tyrosine phosphorylationFocus formation assayPDGF β-receptorDimerization domainHomodimeric proteinTyrosine phosphorylationGenetic methodsGlutamine residuesActive chimerasΒ receptorActive orientationFormation assaysProtein helicesProteinPosition 17ReceptorsPhosphorylation
2000
The platelet-derived growth factor ß receptor as a target of the bovine papillomavirus E5 protein
DiMaio D, Lai C, Mattoon D. The platelet-derived growth factor ß receptor as a target of the bovine papillomavirus E5 protein. Cytokine & Growth Factor Reviews 2000, 11: 283-293. PMID: 10959076, DOI: 10.1016/s1359-6101(00)00012-5.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBovine papillomavirus 1CattleCell Transformation, ViralModels, MolecularMolecular Sequence DataMutationOncogene Proteins, ViralReceptor, Platelet-Derived Growth Factor betaConceptsE5 proteinBovine papillomavirus E5 proteinSH2 domain-containing proteinsCellular signal transduction pathwaysDomain-containing proteinsSignal transduction complexSignal transduction pathwaysLigand-independent fashionGrowth factor receptor activitySpecific transmembraneTransduction complexCytoplasmic domainTransmembrane proteinTransduction pathwaysReceptor dimerizationTyrosine residuesAmino acidsProteinViral transformationDirect interactionBovine papillomavirusUnique mechanismStable complexesComplex formationNew insightsBovine Papillomavirus E5 Protein Induces the Formation of Signal Transduction Complexes Containing Dimeric Activated Platelet-derived Growth Factor β Receptor and Associated Signaling Proteins*
Lai C, Henningson C, DiMaio D. Bovine Papillomavirus E5 Protein Induces the Formation of Signal Transduction Complexes Containing Dimeric Activated Platelet-derived Growth Factor β Receptor and Associated Signaling Proteins*. Journal Of Biological Chemistry 2000, 275: 9832-9840. PMID: 10734138, DOI: 10.1074/jbc.275.13.9832.Peer-Reviewed Original ResearchMeSH KeywordsBovine papillomavirus 1Cell LineCell Transformation, ViralDimerizationOncogene Proteins, ViralPrecipitin TestsReceptor, Platelet-Derived Growth Factor betaSignal TransductionConceptsBovine papillomavirus E5 proteinE5 proteinPDGF beta receptorBeta receptor complexCellular platelet-derived growth factor (PDGF) beta receptorReceptor complexPlatelet-derived growth factor beta receptorPlatelet-derived growth factor β receptorRas-GTPase activating proteinAssembly of multiproteinSignal transduction complexGrowth factor β receptorGrowth factor beta receptorCell growth transformationTransduction complexBeta receptorsP85 subunitSignaling proteinsPhospholipase CgammaActivating proteinReceptor dimersConstitutive activationInactive receptorProteinReceptor molecules
1999
The Bovine Papillomavirus E5 Protein Requires a Juxtamembrane Negative Charge for Activation of the Platelet-Derived Growth Factor β Receptor and Transformation of C127 Cells
Klein O, Kegler-Ebo D, Su J, Smith S, DiMaio D. The Bovine Papillomavirus E5 Protein Requires a Juxtamembrane Negative Charge for Activation of the Platelet-Derived Growth Factor β Receptor and Transformation of C127 Cells. Journal Of Virology 1999, 73: 3264-3272. PMID: 10074180, PMCID: PMC104090, DOI: 10.1128/jvi.73.4.3264-3272.1999.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesCattleCell Transformation, ViralCOS CellsMiceMolecular Sequence DataMutationOncogene Proteins, ViralReceptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorStatic ElectricityConceptsPlatelet-derived growth factor beta receptorPDGF beta receptorGrowth factor beta receptorE5 proteinBovine papillomavirus E5 proteinCell transformationHomodimeric transmembrane proteinSustained receptor activationC127 mouse fibroblastsExtracellular juxtamembrane regionBeta receptorsE5 dimerE5 mutantsDouble mutantJuxtamembrane regionTransmembrane proteinC127 cellsC-terminusAcidic residuesE5 geneMutantsPosition 33Mouse fibroblastsProteinSalt bridge
1998
Bovine papillomavirus E5 protein induces oligomerization and trans-phosphorylation of the platelet-derived growth factor β receptor
Lai C, Henningson C, DiMaio D. Bovine papillomavirus E5 protein induces oligomerization and trans-phosphorylation of the platelet-derived growth factor β receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 15241-15246. PMID: 9860953, PMCID: PMC28027, DOI: 10.1073/pnas.95.26.15241.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsBovine papillomavirus 1CattleCell LineCell Line, TransformedCross-Linking ReagentsDimerizationHumansKineticsMacromolecular SubstancesMiceOncogene Proteins, ViralPhosphorylationProtein-Tyrosine KinasesReceptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorRecombinant ProteinsSequence DeletionTransfectionConceptsBovine papillomavirus E5 proteinE5 proteinPDGF beta receptorCellular platelet-derived growth factor (PDGF) beta receptorKinase-negative mutant receptorPlatelet-derived growth factor beta receptorPlatelet-derived growth factor β receptorChemical cross-linking experimentsGrowth factor β receptorConstitutive tyrosine phosphorylationGrowth factor beta receptorLigand-independent fashionCross-linking experimentsReceptor tyrosine kinasesStable complexesExtracts of cellsPDGF beta-receptor activationIntramolecular autophosphorylationBeta receptorsCoimmunoprecipitation experimentsTransmembrane proteinReceptor activationTyrosine phosphorylationReceptor dimerizationMutant receptorsStructural models of the bovine papillomavirus E5 protein
Surti T, Klein O, Aschheim K, DiMaio D, Smith S. Structural models of the bovine papillomavirus E5 protein. Proteins Structure Function And Bioinformatics 1998, 33: 601-612. PMID: 9849943, DOI: 10.1002/(sici)1097-0134(19981201)33:4<601::aid-prot12>3.0.co;2-i.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsAnimalsCattleComputer SimulationDimerizationKineticsModels, MolecularOncogene Proteins, ViralProtein ConformationProtein Structure, SecondaryReceptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorSpectroscopy, Fourier Transform InfraredConceptsBovine papillomavirus E5 proteinE5 dimerE5 proteinType II integral membrane proteinIntegral membrane proteinsPrevious mutagenesis studiesLigand-independent activationDisulfide-linked homodimerPDGF beta receptorMembrane proteinsTransmembrane orientationMutagenesis studiesMembrane bilayerCell transformationGenetic resultsProteinGln17Receptor moleculesMolecular scaffoldsComplex formationAsp33Computational searchDimerizationDimer structureDimersA single amino acid substitution in a WW‐like domain of diverse members of the PDGF receptor subfamily of tyrosine kinases causes constitutive receptor activation
Irusta P, DiMaio D. A single amino acid substitution in a WW‐like domain of diverse members of the PDGF receptor subfamily of tyrosine kinases causes constitutive receptor activation. The EMBO Journal 1998, 17: 6912-6923. PMID: 9843497, PMCID: PMC1171039, DOI: 10.1093/emboj/17.23.6912.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SequenceAmino Acid SubstitutionAnimalsBinding SitesCell Line, TransformedCloning, MolecularDimerizationEnzyme ActivationHumansInterleukin-3LigandsMiceMolecular Sequence DataMutagenesis, Site-DirectedPeptidesPhosphorylationPolymerase Chain ReactionReceptor Protein-Tyrosine KinasesReceptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorSequence Homology, Amino AcidStructure-Activity RelationshipTyrosineValineConceptsTyrosine kinase activityKinase activityTyrosine kinasePlatelet-derived growth factor beta receptorCytoplasmic juxtamembrane domainPDGF receptorSignal transduction proteinsWW-like domainTransmembrane receptor tyrosine kinaseProtein-protein interactionsBa/F3 cellsGST fusion proteinSingle amino acid substitutionConstitutive receptor activationGrowth factor beta receptorAbsence of ligandReceptor tyrosine kinasesAmino acid substitutionsSequence PPXYTransduction proteinsWW domainsCellular functionsJuxtamembrane regionTyrosine phosphorylationAlanine substitutionsRole of Glutamine 17 of the Bovine Papillomavirus E5 Protein in Platelet-Derived Growth Factor β Receptor Activation and Cell Transformation
Klein O, Polack G, Surti T, Kegler-Ebo D, Smith S, DiMaio D. Role of Glutamine 17 of the Bovine Papillomavirus E5 Protein in Platelet-Derived Growth Factor β Receptor Activation and Cell Transformation. Journal Of Virology 1998, 72: 8921-8932. PMID: 9765437, PMCID: PMC110309, DOI: 10.1128/jvi.72.11.8921-8932.1998.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBovine papillomavirus 1CattleCell LineCell Transformation, ViralCOS CellsDimerizationGenes, ViralGlutamineModels, MolecularMutationOncogene Proteins, ViralProtein ConformationReceptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorConceptsBovine papillomavirus E5 proteinPDGF beta receptorE5 proteinTransform cellsCellular platelet-derived growth factor (PDGF) beta receptorAmino acidsBa/F3 hematopoietic cellsPosition 17Cell transformationPlatelet-derived growth factor beta receptorHomodimeric transmembrane proteinReceptor tyrosine phosphorylationGrowth factor beta receptorReceptor tyrosine kinasesPDGF receptor tyrosine kinaseReceptor activationPossible amino acidsBeta receptorsStable complexesComplex formationMutant proteinsTransmembrane domainTransmembrane proteinGrowth factor-beta (TGF-beta) receptor activationTyrosine phosphorylationVIROCRINE TRANSFORMATION: The Intersection Between Viral Transforming Proteins and Cellular Signal Transduction Pathways
DiMaio D, Lai C, Klein O. VIROCRINE TRANSFORMATION: The Intersection Between Viral Transforming Proteins and Cellular Signal Transduction Pathways. Annual Review Of Microbiology 1998, 52: 397-421. PMID: 9891803, DOI: 10.1146/annurev.micro.52.1.397.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Polyomavirus TransformingBovine papillomavirus 1CattleCell Transformation, ViralHerpesvirus 4, HumanMiceOncogene ProteinsReceptor Protein-Tyrosine KinasesReceptor, Platelet-Derived Growth Factor betaReceptors, ErythropoietinReceptors, Platelet-Derived Growth FactorReceptors, Tumor Necrosis FactorSignal TransductionViral Envelope ProteinsViral Matrix ProteinsViral ProteinsConceptsCellular signal transduction pathwaysSignal transduction pathwaysTransduction pathwaysPlatelet-derived growth factor beta receptorPolyoma virus middle T antigenCellular signal transductionViral transforming proteinsCellular signaling pathwaysViral transformationMiddle T antigenGrowth factor beta receptorReceptor tyrosine kinasesTransforming proteinSignal transductionE5 proteinTumor necrosis factor receptorErythropoietin receptorTyrosine kinaseSignaling pathwaysCell transformationDiverse virusesNecrosis factor receptorViral oncoproteinsSpleen focusT antigen
1997
Identification of amino acids in the transmembrane and juxtamembrane domains of the platelet-derived growth factor receptor required for productive interaction with the bovine papillomavirus E5 protein
Petti L, Reddy V, Smith S, DiMaio D. Identification of amino acids in the transmembrane and juxtamembrane domains of the platelet-derived growth factor receptor required for productive interaction with the bovine papillomavirus E5 protein. Journal Of Virology 1997, 71: 7318-7327. PMID: 9311809, PMCID: PMC192076, DOI: 10.1128/jvi.71.10.7318-7327.1997.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBovine papillomavirus 1CattleCell LineCell MembraneErbB ReceptorsHumansInterleukin-3KineticsLeucineLysineMiceMolecular Sequence DataMutagenesis, Site-DirectedOncogene Proteins v-sisOncogene Proteins, ViralPoint MutationPolymerase Chain ReactionProtein Structure, SecondaryRatsReceptor, ErbB-2Receptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorReceptors, VirusRecombinant Fusion ProteinsRetroviridae Proteins, OncogenicSequence AlignmentThreonineTransfectionConceptsBovine papillomavirus E5 proteinE5 proteinTransmembrane domainPDGF beta receptorAmino acidsCellular platelet-derived growth factor (PDGF) beta receptorReceptor mutantsJuxtamembrane domainPlatelet-derived growth factor beta receptorPutative transmembrane domainsMurine Ba/F3 cellsCarboxyl-terminal domainBa/F3 cellsV-sisReceptor tyrosine phosphorylationExtracellular juxtamembrane domainGrowth factor beta receptorSpecific amino acidsProductive interactionReceptor activationPlatelet-derived growth factor receptorAcidic amino acidsComplex formationThreonine residuesBeta receptorsVirocrine transformation
Drummond-Barbosa D, DiMaio D. Virocrine transformation. Biochimica Et Biophysica Acta 1997, 1332: m1-m17. PMID: 9061007, DOI: 10.1016/s0304-419x(96)00034-0.Peer-Reviewed Original ResearchAntigens, Viral, TumorCell Transformation, ViralGrowth SubstancesOncogene Proteins, ViralPhosphorylationReceptor Protein-Tyrosine KinasesReceptor, IGF Type 1Receptor, Platelet-Derived Growth Factor betaReceptors, ErythropoietinReceptors, Growth FactorReceptors, Platelet-Derived Growth FactorReceptors, Tumor Necrosis FactorSignal TransductionTerminology as TopicViral Envelope ProteinsViral Matrix ProteinsViral ProteinsVirus Replication
1995
Mutational analysis of the interaction between the bovine papillomavirus E5 transforming protein and the endogenous beta receptor for platelet-derived growth factor in mouse C127 cells
Nilson L, Gottlieb R, Polack G, DiMaio D. Mutational analysis of the interaction between the bovine papillomavirus E5 transforming protein and the endogenous beta receptor for platelet-derived growth factor in mouse C127 cells. Journal Of Virology 1995, 69: 5869-5874. PMID: 7543592, PMCID: PMC189463, DOI: 10.1128/jvi.69.9.5869-5874.1995.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesBovine papillomavirus 1Cell LineDNA Mutational AnalysisDown-RegulationFrameshift MutationKineticsMiceMolecular Sequence DataMutagenesisMutagenesis, Site-DirectedOncogene Proteins, ViralPhosphotyrosinePoint MutationProtein-Tyrosine KinasesReceptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorRecombinant ProteinsTyrosineConceptsMouse C127 cellsE5 proteinReceptor tyrosine phosphorylationTyrosine phosphorylationPDGF beta receptorC127 cellsPDGF receptorWild-type E5 proteinBovine papillomavirus E5 proteinCarboxyl-terminal cysteine residueCell transformationPlatelet-derived growth factor beta receptorMembrane-associated proteinsSustained receptor activationPDGF receptor activationMutation of glutamineTransformation-competent mutantsGrowth factor beta receptorBovine papillomavirus E5Carboxyl-terminal positionBeta receptorsHigh-level expressionPlatelet-derived growth factorStable complex formationReceptor activation