Fyn Mediates Leptin Actions in the Thymus of Rodents 英文参考文献.docVIP

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Fyn Mediates Leptin Actions in the Thymus of Rodents 英文参考文献.doc

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Fyn Mediates Leptin Actions in the Thymus of Rodents 英文参考文献

FynMediatesLeptinActionsintheThymusofRodents AlessandraGirasol1,GabrielaG.Albuquerque1,EliMansour1,ElianaP.Arau′jo2,GiovannaDegasperi1, RaphaelG.Denis1,Jose′ B.Carvalheira1,Ma′rioJ.Saad1,L?′cioA.Velloso1* 1DepartmentofInternalMedicine,UniversityofCampinas,Campinas,Brazil,2DepartmentofNursing,UniversityofCampinas,Campinas,Brazil Abstract Background: Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosisinthethymus.Surprisingly,someoftheseeffectsaredependentonsignaltransductionthroughtheIRS1/PI3- kinase,butnotontheactivationofJAK2.Sinceallthewellknowneffectsofleptinindifferentcelltypesandtissuesseemto be dependent on JAK2 activation, we hypothesized that, at least for the control of thymic function, another, unknown kinasecouldmediatethetransductionoftheleptinsignalfromtheObRtowardstheIRS1/PI3-kinasesignalingcascade. Methodology/Principal Findings: Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosinekinase,Fyn,isconstitutivelyassociatedwiththeObRinthymiccells.Followingaleptinstimulus,Fynundergoesan activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activationand,uponFyninhibition,thesignaltransductiontowardsIRS1/PI3-kinaseisabolished.Inaddition,theinhibition ofFynsignificantlymodifiestheeffectsofleptinonthymiccytokineexpression. Conclusion/Significance: Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independentlyofJAK2activation,andmediatessomeoftheimmunomodulatoryeffectsofleptininthistissue. Citation:GirasolA,AlbuquerqueGG,MansourE,Arau′joEP,DegasperiG,etal.(2009)FynMediatesLeptinActionsintheThymusofRodents.PLoSONE4(11): e7707.doi:10.1371/journal.pone.0007707 Editor:Se′rgioTeixeiraFerreira,FederalUniversityofRiodeJaneiro,Brazil ReceivedSeptember4,2009;AcceptedOctober13,2009;PublishedNovember3,2009 Copyright: ? 2009 Girasol et al. This is an open-access article di