Evolution of JAK-STAT Pathway Components Mechanisms and Role in Immune System Development 英文参考文献.docVIP

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Evolution of JAK-STAT Pathway Components Mechanisms and Role in Immune System Development 英文参考文献.doc

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Evolution of JAK-STAT Pathway Components Mechanisms and Role in Immune System Development 英文参考文献

EvolutionofJAK-STATPathwayComponents: MechanismsandRoleinImmuneSystemDevelopment CliffordLiongue1,2,LyndaA.O’Sullivan3,MoniqueC.Trengove1,2,AlisterC.Ward1,2 * 1SchoolofMedicine,DeakinUniversity,Victoria,Australia,2StrategicResearchCentreinMolecularMedicalResearch,DeakinUniversity,Victoria,Australia,3Schoolof LifeEnvironmentalSciences,DeakinUniversity,Victoria,Australia Abstract Background:Lyingdownstreamofamyriadofcytokinereceptors,theJanuskinase(JAK)–Signaltransducerandactivator of transcription (STAT) pathway is pivotal for the development and function of the immune system, with additional importantrolesinotherbiologicalsystems.Togainfurtherinsightintoimmunesystemevolution,wehaveperformeda comprehensivebioinformaticanalysisoftheJAK-STATpathwaycomponents,includingthekeynegativeregulatorsofthis pathway,theSH2-domaincontainingtyrosinephosphatase(SHP),ProteininhibitorsagainstStats(PIAS),andSuppressorof cytokinesignaling(SOCS)proteinsacrossadiverserangeoforganisms. Results: Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additionaldiversity.Incontrast,expansionofupstreamcytokinereceptorsappearstobeapivotaldriverforthedifferential diversificationofspecificpathwaycomponents. Conclusion:DiversificationofJAK-STATpathwaycomponentsduringearlyvertebratedevelopmentoccurredconcurrently withamajorexpansionofupstreamcytokinereceptorsandtworoundsofwholegenomeduplications.Thisproducedan intricatecell-cellcommunicationsystemthathasmadeasignificantcontributiontotheevolutionoftheimmunesystem, particularlytheemergenceofadaptiveimmunity. Citation: Liongue C, O’Sullivan LA, Trengove MC, Ward AC (2012) Evolution of JAK-STAT Pathway Components: Mechanisms and Role in Immune System Development.PLoSONE7(3):e32777.doi:10.1371/journal.pone.0032777 Editor:ShreeRamSingh,NationalCancerInstitute,UnitedStatesofAmerica ReceivedJanua