IL-7isakeycytokineintheimmunesystem,essentialfornormaldevelopmentofBcellsandTcells.MicewiththeIL-7receptordeletedlackBandTcells.SomehumanswithSCID(severecombinedimmunodeficiencydisease)alsohavemutationoftheirIL-7receptorgeneleADIngtoanabsenceofTcellsandgreatlyimpairedBcellproduction.TheIL-7receptorincludestwopolypeptides,agammachainandanalphachain.Thealpha-chainisuniquetotheIL-7receptorwhileseveralothercytokinesusethesamegammareceptorchainasIL-7,includingIL-2,IL-4,IL-9,IL-15andIL-21.BindingofIL-7tothealphachainleadstodimerizationofthealphaandgammachains.JAK3associatedwiththegammachaintyrosinephosphorylatesthealphachainafterdimerization.TheimportanceofJAK3inIL-7signalingissupportedbythesimilarityoftheimmunedefectsinJAK3knockoutmiceandIL-7knockoutmice.Thephosphorylatedalphachainservesasthesiteforrecruitingothersignalingmoleculestothecomplextobephosphorylatedandactivated,includingSTAT5,srckinases,PI3kinase,Pyk2andBcl2proteins.SometargetsofIL-7signalingcontributetocellularsurvival,includingBcl2andPyk2.Othertargetscontributetocellularproliferation,includingPI3kinase,srcfamilykinases(lckandfyn)andSTAT5.ThetranscriptionfactorSTAT5contributestoactivationofmultipledifferentdownstreamgenesinBandTcellsandmaycontributetoVDJrecombinationthroughalterationofchromatinstructure.ThecellsurvivalandcellproliferationsignalsinducedbyIL-7combinetoinducenormalBandTcelldevelopment.

Contributor:GlennCroston,PhD,JiaqianHung

REFERENCES:Baird,A.M.,Thomis,D.C.,Berg,L.J.(1998)TcelldevelopmentandactivationinJak3-deficientmice.J.Leukoc.Biol.63(6),669-77Benbernou,N.,Muegge,K.,Durum,S.K.(2000)Interleukin(IL)-7inducesrapidactivationofPyk2,whichisboundtoJanuskinase1andIL-7Ralpha.J.Biol.Chem.275(10),7060-5.Foxwell,B.M.etal.(1995)Interleukin-7caninducetheactivationofJak1,Jak3andSTAT5proteinsinmurineTcells.Eur.J.Immunol.25(11),3041-6.Fry,T.J.andMackall,C.J.(2002)Interleukin-7:frombenchtoclinic.Blood.99(11),3892-904.Sharfe,N.,Dadi,H.K.,Roifman,C.M.(1995)JAK3proteintyrosinekinasemediatesinterleukin-7-inducedactivationofphosphatidylinositol-3kinase.Blood86(6),2077-85.Zeng,Y.X.,TakahashiH,ShabataM.,Hirokawa,K.(1994)JAK3januskinaseisinvolvedininterleukin7signalingpathway.FEBSLett353(3):289-93.

================  蚂蚁淘在线  ================

免责声明：本文仅代表作者个人观点，与本网无关。其创作性以及文中陈述文字和内容未经本站证实，对本文以及其中全部或者部分内容、文字的真实性、完整性、及时性本站不做任何保证或承诺，请读者仅作参考，并请自行核实相关内容

版权声明：未经蚂蚁淘在线授权不得转载、摘编或利用其他方式使用上述作品。已经经本网授权使用作品的，应该授权范围内使用，并注明“来源：蚂蚁淘在线”。违反上述声明者，本网将追究其相关法律责任。