Interleukin-6(IL-6)isacytokinethatprovokesabroadrangeofcellularandphysiologicalresponses.Inadditiontoplayingaroleininflammationandhematopoiesis,IL-6isinvolvedinotherprocessessuchasneuronaldifferentiationandboneloss.ToproducetheseeffectsIL-6signalsthroughareceptorcomposedoftwodifferentsubunits,analphasubunitthatproducesligandspecificityandgp130,areceptorsubunitsharedincommonwithothercytokinesintheIL-6family.BindingofIL-6toitsreceptorinitiatescellulareventsincludingactivationofJAKkinasesandactivationofras-mediatedsignaling.ActivatedJAKkinasesphosphorylateandactivateSTATtranscriptionfactors,particularlySTAT3,thatmoveintothenucleustoactivatetranscriptionofgenescontainingSTAT3responseelements.Theras-mediatedpathway,actingthroughShc,Grb-2andSos-1upstreamandactivatingMapkinasesdownstream,activatestranscriptionfactorssuchasELK-1andNF-IL-6(C/EBP-beta)thatcanactthroughtheirowncognateresponseelementsinthegenome.ThesefactorsandothertranscriptionfactorslikeAP-1andSRF(serumresponsefactor)thatrespondtomanydifferentsignalingpathwayscometogethertoregulateavarietyofcomplexpromotersandenhancersthatrespondtoIL-6andothersignalingfactors. Contributor:GlennCroston,PhD. REFERENCES:
