Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF‐1‐induced macrophage migration

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

关键词: protein kinases/phosphatases;    chemotaxis;    invasion;    signal transduction;   

DOI  :  10.1189/jlb.2A0815-344RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Amajorroleofcolony‐stimulatingfactor‐1istostimulatethedifferentiationofmononuclearphagocyticlineagecellsintoadherent,motile,maturemacrophages.Thecolony‐stimulatingfactor‐1receptortransducescolony‐stimulatingfactor‐1signaling,andwehaveshownpreviouslythatphosphatidylinositol3‐kinasep110δisacriticalmediatorofcolony‐stimulatingfactor‐1–stimulatedmotilitythroughthecolony‐stimulatingfactor‐1receptorpY721motif.Srcfamilykinasesarealsoimplicatedintheregulationofmacrophagemotilityandincolony‐stimulatingfactor‐1receptorsignaling,althoughfunctionalredundancyofthemultipleSFKsexpressedinmacrophagesmakesitchallengingtodelineatetheirspecificfunctions.WereportacomprehensiveanalysisofindividualSrcfamilykinaseexpressioninmacrophagecelllinesandprimarymacrophagesanddemonstratecolony‐stimulatingfactor‐1–inducedchangesinSrcfamilykinasesubcellularlocalization,whichprovidescluestotheirdistinctandredundantfunctionsinmacrophages.Moreover,expressionofindividualSrcfamilykinasesisbothspeciesspecificanddependentoncolony‐stimulatingfactor‐1–inducedmacrophagedifferentiation.Hckassociatedwiththeactivatedcolony‐stimulatingfactor‐1receptor,whereasLynassociatedwiththereceptorinaconstitutivemanner.Consistentwiththis,inhibitorstudiesrevealedthatSrcfamilykinaseswereimportantforbothcolony‐stimulatingfactor‐1receptoractivationandcolony‐stimulatingfactor‐1–inducedmacrophagespreading,motility,andinvasion.Distinctcolony‐stimulatingfactor‐1–inducedchangesinthesubcellularlocalizationofindividualSFKssuggestspecificrolesfortheseSrcfamilykinasesinthemacrophageresponsetocolony‐stimulatingfactor‐1...

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