Ecto-Phosphorylation of CD98 Regulates Cell-Cell Interactions 英文参考文献.docVIP

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Ecto-Phosphorylation of CD98 Regulates Cell-Cell Interactions 英文参考文献.doc

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Ecto-Phosphorylation of CD98 Regulates Cell-Cell Interactions 英文参考文献

Ecto-PhosphorylationofCD98RegulatesCell-Cell Interactions HangThiThuNguyen*,GuillaumeDalmasso,YutaoYan,TracyS.Obertone,ShanthiV.Sitaraman,Didier Merlin DivisionofDigestiveDiseases,DepartmentofMedicine,EmoryUniversitySchoolofMedicine,Atlanta,Georgia,UnitedStatesofAmerica Abstract Ecto-phosphorylationplaysanimportantroleinmanycellularfunctions.ThetransmembraneglycoproteinCD98contains potentialphosphorylationsitesinitsextracellularC-terminaltail.Wehypothesizedthatextracellularsignalingthroughecto- proteinkinases(ePKs)mightleadtoecto-phosphorylationofCD98andinfluenceitsmultiplefunctions,includingitsrolein cell-cellinteractions.OurresultsshowthatrecombinantCD98wasphosphorylatedinvitrobyePKsfromJurkatcellsandby the commercial casein kinase 2 (CK2). Alanine substitutions at serines-305/307/309 or serines-426/430 attenuated CK2- mediated CD98 phosphorylation, suggesting that these residues are the dominant phosphorylation sites for CK2. Furthermore, CD98 expressed in the basolateral membranes of intestinal epithelial Caco2-BBE cells was ecto- phosphorylated by Jurkat cell-derived ePKs and ecto-CK2 was involved in this process. Importantly, cell attachment studiesshowedthattheecto-phosphorylationofCD98enhancedheterotypiccell-cellinteractionsandthattheextracellular domainofCD98,whichpossessestheserinephosphorylationsites,wascrucialforthiseffect.Inaddition,phosphorylationof recombinantCD98increaseditsinteractionswithJurkatandCaco2-BBEcells,andpromotedcellattachmentandspreading. Inconclusion,herewedemonstratedtheecto-phosphorylationofCD98byePKsanditsfunctionalimportanceincell-cell interactions.OurfindingsrevealanovelmechanisminvolvedinregulatingthemultiplefunctionsofCD98andraiseCD98as apromisingtargetfortherapeuticmodulationsofcell-cellinteractions. Citation:NguyenHTT,DalmassoG,YanY,ObertoneTS,SitaramanSV,etal.(2008)Ecto-PhosphorylationofCD98RegulatesCell-CellInteractions.PLoSONE3(12): e3895.doi:10.1371/journal.pone.0003895 Editor:WenqingXu,UniversityofWashington,UnitedState