2016
Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation
Zou S, Teixeira AM, Yin M, Xiang Y, Xavier-Ferrucio J, Zhang PX, Hwa J, Min W, Krause DS. Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation. Thrombosis And Haemostasis 2016, 116: 506-516. PMID: 27345948, PMCID: PMC5845781, DOI: 10.1160/th15-11-0848.Peer-Reviewed Original ResearchConceptsMegakaryocyte maturationPlatelet functionRhoA activationKO plateletsLeukemia-associated Rho guanineΑ-granule releasePlatelet signal transductionSmall molecule-mediated inhibitionExchange factorSignal transductionMyosin light chain phosphorylationRho guanineKO miceBleeding timeHuman megakaryocytesInternal bleedingPlatelet aggregationNormal haemostasisLight chain phosphorylationHuman plateletsVivo assaysPlateletsSpecific roleMiceChain phosphorylation
2012
Induction of megakaryocyte differentiation drives nuclear accumulation and transcriptional function of MKL1 via actin polymerization and RhoA activation
Smith EC, Teixeira AM, Chen RC, Wang L, Gao Y, Hahn KL, Krause DS. Induction of megakaryocyte differentiation drives nuclear accumulation and transcriptional function of MKL1 via actin polymerization and RhoA activation. Blood 2012, 121: 1094-1101. PMID: 23243284, PMCID: PMC3575755, DOI: 10.1182/blood-2012-05-429993.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell DifferentiationCell Line, TumorCell NucleusDNA-Binding ProteinsEnzyme ActivationHumansMegakaryocyte Progenitor CellsMegakaryocytesMiceOncogene Proteins, FusionProtein MultimerizationRhoA GTP-Binding ProteinSerum Response FactorTetradecanoylphorbol AcetateThrombopoietinTrans-ActivatorsConceptsMegakaryocyte differentiationActin polymerizationSubcellular localizationSerum response factor (SRF) transcriptional activityRhoA activitySRF target genesComplex cellular responsesFactor transcriptional activityMuscle cell typesCell-type specificHuman erythroleukemia cellsPrimary megakaryocytesTranscriptional regulatorsActin organizationCellular functionsTranscriptional functionSRF activityNuclear localizationTarget genesMegakaryocytic differentiationTranscriptional activityNuclear accumulationErythroleukemia cellsMolecular mechanismsRhoA activationRole of RhoA-Specific Guanine Exchange Factors in Regulation of Endomitosis in Megakaryocytes
Gao Y, Smith E, Ker E, Campbell P, Cheng EC, Zou S, Lin S, Wang L, Halene S, Krause DS. Role of RhoA-Specific Guanine Exchange Factors in Regulation of Endomitosis in Megakaryocytes. Developmental Cell 2012, 22: 573-584. PMID: 22387001, PMCID: PMC3306542, DOI: 10.1016/j.devcel.2011.12.019.Peer-Reviewed Original ResearchConceptsGEF-H1Efficient platelet productionExchange factor GEF-H1Guanine exchange factorGEF-H1 knockdownDevelopment of aneuploidyGEF-H1 expressionMK polyploidizationExchange factorPloidy defectsAberrant mitosisDevelopmental processesExogenous expressionPolyploidizationRhoA activationEndomitotic cyclePrimary cellsUnknown mechanismMechanistic insightsECT2EndomitosisAneuploid cancersPlatelet productionMegakaryocytesDownregulation