2021
In vitro fluorescence assay to measure GDP/GTP exchange of guanine nucleotide exchange factors of Rho family GTPases
Blaise AM, Corcoran EE, Wattenberg ES, Zhang YL, Cottrell JR, Koleske AJ. In vitro fluorescence assay to measure GDP/GTP exchange of guanine nucleotide exchange factors of Rho family GTPases. Biology Methods And Protocols 2021, 7: bpab024. PMID: 35087952, PMCID: PMC8789339, DOI: 10.1093/biomethods/bpab024.Peer-Reviewed Original ResearchNucleotide exchange factorsGEF domainExchange factorGuanine nucleotide exchange factorsGDP/GTP exchangeRho family GEFsActivation of GTPasesFluorescence-based analysisRare variantsGTP loadingGTP exchangeRho familyHigh-throughput screeningWhole-exome sequencingCellular activitiesGenetic variantsGTPasesGEFExome sequencingCritical roleUser-friendly protocolComplete understandingHuman developmentVariantsGEFs
2018
Multiplexed Real-Time NMR GTPase Assay for Simultaneous Monitoring of Multiple Guanine Nucleotide Exchange Factor Activities from Human Cancer Cells and Organoids
Gebregiworgis T, Marshall C, Nishikawa T, Radulovich N, Sandí M, Fang Z, Rottapel R, Tsao M, Ikura M. Multiplexed Real-Time NMR GTPase Assay for Simultaneous Monitoring of Multiple Guanine Nucleotide Exchange Factor Activities from Human Cancer Cells and Organoids. Journal Of The American Chemical Society 2018, 140: 4473-4476. PMID: 29543440, DOI: 10.1021/jacs.7b13703.Peer-Reviewed Original ResearchConceptsGuanine nucleotide exchange factorsRhoA-specific Guanine Nucleotide Exchange FactorGuanine nucleotide exchange factor activityNucleotide exchange factor activityHigher GEF activityNucleotide exchange factorsImportant cellular functionsExchange factor activityExchange of GTPProtein of interestReal-time NMRRNA-seq dataCultured human cellsGEF assaysHuman cancer cellsSmall GTPasesExchange factorGEF activityCellular functionsIsotopic labeling schemesNucleotide exchangeGEF-H1GTPase assaysFunctional analysisHuman cells
2017
A Phosphoproteomic Screen Identifies a Guanine Nucleotide Exchange Factor for Rab3A Protein as a Mitogen-activated Protein (MAP) Kinase Phosphatase-5-regulated MAP Kinase Target in Interleukin 6 (IL-6) Secretion and Myogenesis*
Lee H, Min K, Yi JS, Shi H, Chang W, Jackson L, Bennett AM. A Phosphoproteomic Screen Identifies a Guanine Nucleotide Exchange Factor for Rab3A Protein as a Mitogen-activated Protein (MAP) Kinase Phosphatase-5-regulated MAP Kinase Target in Interleukin 6 (IL-6) Secretion and Myogenesis*. Journal Of Biological Chemistry 2017, 292: 3581-3590. PMID: 28096466, PMCID: PMC5339744, DOI: 10.1074/jbc.m116.769208.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnimalsCell MovementCell ProliferationDual-Specificity PhosphatasesGene Expression Regulation, EnzymologicGuanine Nucleotide Exchange FactorsInterleukin-6MAP Kinase Signaling SystemMiceMice, KnockoutMuscle DevelopmentMuscle, SkeletalMutationMyoblastsPhosphorylationProteomicsrab3A GTP-Binding ProteinRegenerationSerineConceptsMitogen-activated protein kinaseMAPK phosphatase-5MAPK substratesExchange factorSer-169Guanine nucleotide exchange factorsNucleotide exchange factorsPhosphorylation-defective mutantSkeletal muscleP38 mitogen-activated protein kinaseC-Jun N-terminal kinaseMAPK-dependent signalingN-terminal kinaseSkeletal muscle functionSubstrate screenMAPK targetsSerine 169Rab3A proteinScreen identifiesRegenerative myogenesisPhosphatase 5Protein kinaseKinase targetsC2C12 myoblastsNegative regulator
2013
Control of the G- protein cascade dynamics by GDP dissociation inhibitors
Nikonova E, Tsyganov MA, Kolch W, Fey D, Kholodenko BN. Control of the G- protein cascade dynamics by GDP dissociation inhibitors. Molecular Omics 2013, 9: 2454-2462. PMID: 23872884, DOI: 10.1039/c3mb70152b.Peer-Reviewed Original ResearchConceptsGDP dissociation inhibitorGuanine nucleotide exchange factorsRho family GTPasesDissociation inhibitorNucleotide exchange factorsKey cellular processesProtrusion-retraction cyclesSignal-induced changesCell migration behaviorActive GTPExchange factorInactive GDPCellular processesGTPase activityRac1 activityGTPasesBistable switchRhoADistinct modesRhoGDI1GTPaseInhibitorsRac1GTPCytoplasm
2011
Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate
Wu X, Bradley MJ, Cai Y, Kümmel D, De La Cruz EM, Barr FA, Reinisch KM. Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 18672-18677. PMID: 22065758, PMCID: PMC3219131, DOI: 10.1073/pnas.1110415108.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBiological TransportCrystallography, X-RayDeath Domain Receptor Signaling Adaptor ProteinsGuanineGuanine Nucleotide Exchange FactorsHumansKineticsNucleotidesProtein BindingProtein Structure, SecondaryProtein Structure, Tertiaryrab GTP-Binding Proteinsrab1 GTP-Binding ProteinsConceptsGuanine nucleotide exchange factorsDENN domain proteinsMembrane traffic pathwaysNucleotide exchange factorsGDP-bound formGTP-bound formSwitch regions IHigher eukaryotesRab GTPasesGEF familyEukaryotic cellsTraffic pathwaysExchange factorSwitch INucleotide bindingKey regulatorConformational changesFirst structureNovel insightsRab35ProteinDENND1BEukaryotesRegion IGTPases
2010
Cell adhesion: integrating cytoskeletal dynamics and cellular tension
Parsons JT, Horwitz AR, Schwartz MA. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nature Reviews Molecular Cell Biology 2010, 11: 633-643. PMID: 20729930, PMCID: PMC2992881, DOI: 10.1038/nrm2957.Peer-Reviewed Original ResearchConceptsRho GTPasesGuanine nucleotide exchange factorsNucleotide exchange factorsGTPase-activating proteinsMyosin II activityActin-myosin contractionCytoskeletal dynamicsActin cytoskeletonCellular tensionExchange factorRho proteinsProtein TyrAdhesion dynamicsMorphogenetic processesCell rearAdhesion sizeCell frontIntegrin clusteringActin polymerizationRho activationMyosin IIDownstream signalingFeedback loopCell migrationComplex feedback loops
2006
The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor
Murata T, Delprato A, Ingmundson A, Toomre DK, Lambright DG, Roy CR. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nature Cell Biology 2006, 8: 971-977. PMID: 16906144, DOI: 10.1038/ncb1463.Peer-Reviewed Original ResearchConceptsGuanine nucleotide exchange factorsNucleotide exchange factorsType IV secretion apparatusIntracellular pathogen Legionella pneumophilaHost cellsEndoplasmic reticulum-derived vesiclesDot/IcmPathogen Legionella pneumophilaL. pneumophila mutantsRab1 recruitmentSubstrate proteinsRab familyExchange factorGTPase Rab1Secretion apparatusVesicular transportBacterial proteinsGolgi apparatusVisual screenEndoplasmic reticulumRab1Membrane transportSpecific membersDrrAIntracellular pathogens
2005
P-Rex1 Is a Primary Rac2 Guanine Nucleotide Exchange Factor in Mouse Neutrophils
Dong X, Mo Z, Bokoch G, Guo C, Li Z, Wu D. P-Rex1 Is a Primary Rac2 Guanine Nucleotide Exchange Factor in Mouse Neutrophils. Current Biology 2005, 15: 1874-1879. PMID: 16243036, DOI: 10.1016/j.cub.2005.09.014.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCaseinsCell LineChemotaxisCloning, MolecularEnzyme ActivationGene TargetingGuanine Nucleotide Exchange FactorsHumansImmunoprecipitationMiceMice, KnockoutN-Formylmethionine Leucyl-PhenylalanineNeuropeptidesNeutrophilsProtein Transportrac GTP-Binding Proteinsrac1 GTP-Binding ProteinSuperoxidesConceptsP-Rex1Exchange factorGuanine nucleotide exchange factorsNucleotide exchange factorsRegulation of RacF-actin formationMouse neutrophilsSmall GTPasesRho familyRac activityApparent high affinityRac activatorActin formationRac1 activationRac2 activationCdc42Mouse linesRacRac2RhoAMigration rateRegulationHigh affinityLeukocyte chemoattractantsGTPases
2004
GEFT, A Rho Family Guanine Nucleotide Exchange Factor, Regulates Neurite Outgrowth and Dendritic Spine Formation*
Bryan B, Kumar V, Stafford L, Cai Y, Wu G, Liu M. GEFT, A Rho Family Guanine Nucleotide Exchange Factor, Regulates Neurite Outgrowth and Dendritic Spine Formation*. Journal Of Biological Chemistry 2004, 279: 45824-45832. PMID: 15322108, DOI: 10.1074/jbc.m406216200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalscdc42 GTP-Binding ProteinCells, CulturedGuanine Nucleotide Exchange FactorsHumansNeuritesNF-kappa Bp21-Activated KinasesProtein Serine-Threonine Kinasesrac1 GTP-Binding ProteinRatsRats, Sprague-DawleyRho Guanine Nucleotide Exchange FactorsTranscription Factor AP-1Transcriptional ActivationConceptsGuanine nucleotide exchange factorsNucleotide exchange factorsExchange factorRho family guanine nucleotide-exchange factorNeurite outgrowthState of Rac1Dendritic spine formationCell fate determinationActin cytoskeletal organizationExchange of GDPActivation of RacNormal cell growthRac1/Cdc42Spine formationFate determinationEukaryotic cellsGene regulationNeuroblastoma cellsSmall GTPasesActive GTPDbl familyRho familyCellular processesRho GTPasesCytoskeletal organizationThe Novel Cdc42 Guanine Nucleotide Exchange Factor, Zizimin1, Dimerizes via the Cdc42-binding CZH2 Domain*
Meller N, Irani-Tehrani M, Ratnikov BI, Paschal BM, Schwartz MA. The Novel Cdc42 Guanine Nucleotide Exchange Factor, Zizimin1, Dimerizes via the Cdc42-binding CZH2 Domain*. Journal Of Biological Chemistry 2004, 279: 37470-37476. PMID: 15247287, DOI: 10.1074/jbc.m404535200.Peer-Reviewed Original ResearchConceptsExchange factorCdc42 Guanine Nucleotide Exchange FactorGuanine nucleotide exchange factorsRho family small GTPasesDomain-containing proteinsNucleotide exchange factorsMultiple cellular processesCDM proteinsCZH proteinsSmall GTPasesRho proteinsCellular processesCdc42 activationRho-GEFsCdc42Acid regionHomology analysisCritical regulatorZizimin1ProteinPositive cooperativityMutation analysisDimerizationDock180GTPasesAbl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation
Sini P, Cannas A, Koleske AJ, Di Fiore PP, Scita G. Abl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation. Nature Cell Biology 2004, 6: 268-274. PMID: 15039778, DOI: 10.1038/ncb1096.Peer-Reviewed Original ResearchConceptsGuanine nucleotide exchange factorsSos-1Rac activationTyrosine phosphorylationFunction of RacNon-receptor tyrosine kinase AblActin cytoskeleton remodellingNucleotide exchange factorsRac-GEF activityTyrosine kinase AblActivation of RTKsActivity of RacReceptor tyrosine kinasesCytoskeleton remodellingActin remodellingSignal transductionMolecular connectionMolecular mechanismsTyrosine kinaseBcr-Abl oncoproteinRacPharmacological interferencePhosphorylationGrowth factorABL signals
2002
Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins
Meller N, Irani-Tehrani M, Kiosses WB, Del Pozo MA, Schwartz MA. Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins. Nature Cell Biology 2002, 4: 639-647. PMID: 12172552, DOI: 10.1038/ncb835.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsBinding Sitescdc42 GTP-Binding ProteinCloning, MolecularEnzyme ActivationGuanine Nucleotide Exchange FactorsHumansMiceMolecular Sequence DataProtein Structure, Tertiaryrho GTP-Binding ProteinsRNA, MessengerSequence Homology, Amino AcidTissue DistributionConceptsGuanine nucleotide exchange factorsCdc42 activatorGEF domainRho family GTPases RacNucleotide exchange factorsCDM proteinsRho proteinsRho familyGTPases RacNew superfamilySequence comparisonCdc42 activationNew proteinsMutational analysisGene expressionBiochemical searchCell migrationProteinDirect interactionCdc42Zizimin1RacActivatorGTPasesDomain
1998
Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction
Holsinger L, Graef I, Swat W, Chi T, Bautista D, Davidson L, Lewis R, Alt F, Crabtree G. Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction. Current Biology 1998, 8: 563-573. PMID: 9601640, DOI: 10.1016/s0960-9822(98)70225-8.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell Cycle ProteinsCytoskeletonDNA-Binding ProteinsHumansJurkat CellsMiceNFATC Transcription FactorsNuclear ProteinsProto-Oncogene ProteinsProto-Oncogene Proteins c-vavReceptor-CD3 Complex, Antigen, T-CellReceptors, Antigen, T-CellSignal TransductionT-LymphocytesTranscription FactorsTranscription, GeneticConceptsMitogen-activated protein kinaseCap formationActin polymerizationGuanine nucleotide exchange factorsJun N-terminal kinaseTranscription factor NF-ATc1Vav-deficient miceActin-dependent pathwayStress-activated kinasesGrowth regulatory signalsActin cap formationAntigen receptor signalingEgr-1 geneLymphocyte signal transductionN-terminal kinaseAntigen-receptor interactionActin cytoskeletonExchange factorTranscriptional inductionSignal transductionDependent transcriptionProtein kinaseGTPase RacRegulatory signalsNull mutation
1997
Requirement of Protein Kinase Cζ for Stimulation of Protein Synthesis by Insulin
Mendez R, Kollmorgen G, White M, Rhoads R. Requirement of Protein Kinase Cζ for Stimulation of Protein Synthesis by Insulin. Molecular And Cellular Biology 1997, 17: 5184-5192. PMID: 9271396, PMCID: PMC232369, DOI: 10.1128/mcb.17.9.5184.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCalcium-Calmodulin-Dependent Protein KinasesEnzyme ActivationInsulinInsulin Receptor Substrate ProteinsMiceOligonucleotides, AntisensePhosphatidylinositol 3-KinasesPhosphoproteinsPhosphotransferases (Alcohol Group Acceptor)Protein BiosynthesisProtein Kinase CProtein Serine-Threonine KinasesProto-Oncogene Proteins c-mycRibosomal Protein S6 KinasesConceptsGeneral protein synthesisPKC-zetaCell cycle progressionProtein synthesisIRS-1Insulin receptorCycle progressionGuanine nucleotide exchange factorsNucleotide exchange factorsInsulin-stimulated protein synthesisProto-oncogene AktTarget of rapamycinMitogen-activated protein kinaseInsulin-stimulated activationPKC zeta activationProtein kinase CζGrowth-regulating proteinsActive PKC-zetaPrevention of apoptosisExchange factorPhosphorylated substratesS6 kinaseProtein kinaseGab-1Ectopic expression
1996
Identification of the Binding Site for Acidic Phospholipids on the PH Domain of Dynamin: Implications for Stimulation of GTPase Activity
Zheng J, Cahill S, Lemmon M, Fushman D, Schlessinger J, Cowburn D. Identification of the Binding Site for Acidic Phospholipids on the PH Domain of Dynamin: Implications for Stimulation of GTPase Activity. Journal Of Molecular Biology 1996, 255: 14-21. PMID: 8568861, DOI: 10.1006/jmbi.1996.0002.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBlood ProteinsDynaminsGTP PhosphohydrolasesHumansKineticsMagnetic Resonance SpectroscopyModels, MolecularPhosphatidic AcidsPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositol PhosphatesPhosphoproteinsProtein ConformationSequence Homology, Amino AcidSpectrometry, FluorescenceConceptsDynamin PH domainPH domainMembrane associationGTPase activityGuanine nucleotide exchange factorsNucleotide exchange factorsPleckstrin homology domainAcidic phospholipidsBinding of phospholipidsHomology domainExchange factorHuman dynaminGTP hydrolysisDynaminLipid head groupsLigand interactionsGTPaseBinding sitesPhosphatidylinositolSpecific sitesProteinPhospholipidsRelative affinityBindingDomain
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