2017
SNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume
Zou S, Teixeira AM, Kostadima M, Astle WJ, Radhakrishnan A, Simon LM, Truman L, Fang JS, Hwa J, Zhang PX, van der Harst P, Bray PF, Ouwehand WH, Frontini M, Krause DS. SNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume. PLOS ONE 2017, 12: e0178095. PMID: 28542600, PMCID: PMC5441597, DOI: 10.1371/journal.pone.0178095.Peer-Reviewed Original ResearchConceptsExpression quantitative lociMK maturationGene expressionRho guanine exchange factorsHuman megakaryocytesGenome-wide association studiesDNase I hypersensitive regionGuanine exchange factorHuman genetic studiesExchange factorReporter mouse modelDNase hypersensitivityQuantitative lociPlatelet traitsMK developmentTranscript levelsCausal SNPsHypersensitive regionARHGEF3Human phenotypesAssociation studiesGenetic studiesHematopoietic subpopulationsGenetic variantsSNPs
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
Role 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