Requirement of Transmembrane Domain for CD154 Association to Lipid Rafts and Subsequent Biological Events 英文参考文献.docVIP

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Requirement of Transmembrane Domain for CD154 Association to Lipid Rafts and Subsequent Biological Events 英文参考文献.doc

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Requirement of Transmembrane Domain for CD154 Association to Lipid Rafts and Subsequent Biological Events 英文参考文献

RequirementofTransmembraneDomainforCD154 AssociationtoLipidRaftsandSubsequentBiological Events NadirBenslimane,GhadaS.Hassan,DanielYacoub,WalidMourad* Laboratoired’ImmunologieCellulaireetMole′culaire,CentreHospitalierdel’Universite′ deMontre′al,Ho?pitalSaint-Luc,Montre′al, Quebec,Canada Abstract Interaction of CD40 with CD154 leads to recruitment of both molecules into lipid rafts, resulting in bi-directional cell activation.TheprecisemechanismbywhichCD154istranslocatedintolipidraftsanditsimpactonCD154signalingremain largelyunknown.OuraimistoidentifythedomainofCD154facilitatingitsassociationtolipidraftsandtheimpactofsuch associationonsignalingeventsandcytokineproduction.Thus,wegeneratedJurkatcelllinesexpressingtruncatedCD154 lackingthecytoplasmicdomainorchimericCD154inwhichthetransmembranedomainwasreplacedbythatoftransferrin receptor I, known to be excluded from lipid rafts. Our results show that cell stimulation with soluble CD40 leads to the associationofCD154wild-typeandCD154-truncated,butnotCD154-chimera,withlipidrafts.Thisiscorrelatedwithfailure ofCD154-chimeratoactivateAktandp38MAPkinases,knowneffectorsofCD154signaling.WealsofoundthatCD154- chimeralosttheabilitytopromoteIL-2productionuponTcellstimulationwithanti-CD3/CD28andsolubleCD40.These results demonstrate the implication of the transmembrane domain of CD154 in lipid raft association, and that this associationisnecessaryforCD154-mediatedAktandp38activationwithconsequentenhancementofIL-2production. Citation:BenslimaneN,HassanGS,YacoubD,MouradW(2012)RequirementofTransmembraneDomainforCD154AssociationtoLipidRaftsandSubsequent BiologicalEvents.PLoSONE7(8):e43070.doi:10.1371/journal.pone.0043070 Editor:WanjinHong,InstituteofMolecularandCellBiology,Singapore ReceivedMarch29,2012;AcceptedJuly16,2012;PublishedAugust14,2012 Copyright:?2012Benslimaneetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymediu