CellSignalingTechnology©2003–2016CellSignalingTechnology,Inc.www.cellsignal.comDirectStimulatoryModificationDirectInhibitoryModificationMultistepStimulatoryModificationMultistepInhibitoryModificationTentativeStimulatoryModificationTentativeInhibitoryModificationDirectInhibitoryModificationMultistepStimulatoryModificationMultistepInhibitoryModificationTentativeStimulatoryModificationTranscriptionalInhibitoryModificationKinasePhosphataseTranscriptionFactorCaspaseReceptorEnzymepro-apoptoticpro-survivalGAP/GEFGTPaseG-proteinAcetylaseDeacetylasePathwayDiagramKeyESCPluripotencyandDifferentiationNICDNucleusCytoplasmFrizzledGαq/oErk1/2NanogNICDSox2Oct-4TCFsErk1/2Ras/RafGeneExpressionPluripotencyandSelfRenewalhESCmarkers:GeneExpressionGeneExpressionAktSmad2/3Smad2/3Smad2/3Smad2/3Smad2/3β-cateninβ-cateninβ-cateninSmad4Smad4Smad1/5/9Smad1/5/9Smad1/5/9Smad1/5/9Smad4Smad1/5/9PI3KIGF-IRFGFRTGF-β/Activin/NodalBMPMEK1/2PP2ALRPWntSARAAxinAPCGSK-3γ−SecretasePolycombOct-4Sox2NanogSSEA3/4TRA-1-60TRA-1-81DifferentiationEndodermMesodermEctodermPrimordialGermCellsNotch