Cell Proliferation and Migration Are Modulated by Cdk-1-Phosphorylated Endothelial-Monocyte Activating Polypeptide II 英文参考文献.docVIP

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Cell Proliferation and Migration Are Modulated by Cdk-1-Phosphorylated Endothelial-Monocyte Activating Polypeptide II 英文参考文献.doc

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Cell Proliferation and Migration Are Modulated by Cdk-1-Phosphorylated Endothelial-Monocyte Activating Polypeptide II 英文参考文献

CellProliferationandMigrationAreModulatedbyCdk-1- PhosphorylatedEndothelial-MonocyteActivating PolypeptideII MargaretA.Schwarz*,JanetThornton,HaimingXu,NiranjanAwasthi,RoderichE.Schwarz DepartmentsofPediatricsandSurgery,UniversityofTexasSouthwesternMedicalCenteratDallas,Dallas,Texas,UnitedStatesofAmerica Abstract Background: Endothelial-Monocyte Activating Polypeptide (EMAP II) is a secreted protein with well-established anti- angiogenic activities. Intracellular EMAP II expression is increased during fetal development at epithelial/mesenchymal boundariesandinpathophysiologicfibroproliferativecellsofbronchopulmonarydysplasia,emphysema,andscarfibroblast tissue following myocardial ischemia. Precise function and regulation of intracellular EMAP II, however, has not been exploredtodate. Methodology/PrincipalFindings:HereweshowthathighintracellularEMAPIIsuppressescellularproliferationbyslowing progression through the G2M cell cycle transition in epithelium and fibroblast. Furthermore, EMAP II binds to and is phosphorylatedbyCdk1,andexhibitsnuclear/cytoplasmicpartitioning,withonlynuclearEMAPIIbeingphosphorylated. WeobservedthatextracellularsecretedEMAPIIinducesendothelialcellapoptosis,whereasexcessintracellularEMAPII facilitatesepithelialandfibroblastcellsmigration. Conclusions/Significance: Our findings suggest that EMAP II has specific intracellular effects, and that this intracellular functionappearstoantagonizeitsextracellularanti-angiogeniceffectsduringfetaldevelopment andpulmonarydisease progression. Citation:SchwarzMA,ThorntonJ,XuH,AwasthiN,SchwarzRE(2012)CellProliferationandMigrationAreModulatedbyCdk-1-PhosphorylatedEndothelial- MonocyteActivatingPolypeptideII.PLoSONE7(3):e33101.doi:10.1371/journal.pone.0033101 Editor:ShreeRamSingh,NationalCancerInstitute,UnitedStatesofAmerica ReceivedJanuary20,2012;AcceptedFebruary9,2012;PublishedMarch8,2012 Copyright: ? 2012 Schwarz et al. This is an open-access article distributed under the terms of the Creative Commons