Macrophage differentiation of myeloid progenitor cells in response to M‐CSF is regulated by the dual‐specificity phosphatase DUSP5

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: hematopoiesis;    MAPK;    ERK;    MKP;    CSF‐;    1;    granulocyte;   

DOI  :  10.1189/jlb.0309151

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

M‐CSFregulatestheproduction,survival,andfunctionofmonocytesandmacrophages.TheMAPKsERK1/2arekeyelementsforsignalintegrationdownstreamoftheM‐CSFR,andtheirsustainedactivationisessentialformacrophagedifferentiation.Inthisstudy,wesoughttoisolategeneswhoseinductionbyM‐CSFisdependentonpersistentMAPKactivation,therebybeingpossiblyinvolvedinthecommitmentofmyeloidprogenitorstomacrophagedifferentiation.FollowingSSHbetweencDNAlibrariesfromFD‐FmscellsstimulatedbyM‐CSFfor8hinthepresenceortheabsenceoftheMEKinhibitorU0126,weisolatedDUSP5.DUSP5expressionisinducedbyM‐CSFinvariousmyeloidcellsandactsasaspecificnegative‐feedbackregulatorofERK1/2.InFD‐FmscellsthatproliferateanddifferentiatetowardmacrophagesinresponsetoM‐CSF,overexpressionofDUSP5increasedM‐CSF‐dependentproliferationandstronglydecreaseddifferentiation.Similarly,overexpressionofDUSP5inthemultipotentEGER‐FmscellsnotonlysignificantlyincreasedM‐CSF‐inducedproliferationandpreventedmacrophagedifferentiationbutalsofavoredgranulocyticdifferentiation.Altogether,experimentsdemonstratedthatDUSP5isimplicatedinM‐CSFsignalingandsuggestedthatitmayinfluencemyeloidcellfate...

【 授权许可】

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