Theepidermalgrowthfactor(EGF)peptideinducescellularproliferationthroughtheEGFreceptor,whichhasatyrosinekinasecytoplasmicdomain,asingletransmembranedomainandanextracellulardomaininvolvedinEGFbindingandreceptordimerization.InhibitorsoftheEGFreceptorarebeingpursuedaspotentialcancertherapiesandEGFmaystimulatewoundhealing.MutationoftheEGFreceptorhasbeenassociatedwithcancerinhumans.TheproliferativeeffectsofEGFaresignaledthroughseveralpathways.BindingofEGFresultsinEGFreceptordimerization,autophosphorylationofthereceptor,andtyrosinephosphorylationofotherproteins.TheEGFreceptoractivatesrasandtheMAPkinasepathway,ultimatelycausingphosphorylationoftranscriptionfactorssuchasc-FostocreateAP-1andELK-1thatcontributetoproliferation.ActivationofSTAT-1andSTAT-3transcriptionfactorsbyJAKkinasesinresponsetoEGFcontributestoproliferativesignaling.PhosphatidylinositolsignalingandcalciumreleaseinducedbyEGFactivateproteinkinaseC,anothercomponentofEGFsignaling.CrosstalkofEGFsignalingwithotherpathwaysmaketheEGFreceptorajunctionpointbetweensignalingsystems.

Contributor:GlennCroston,PhD.

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