SmadsarecriticalmediatorsconveyingsignalsfromtheTGF-β-superfamilymemberstothenucleus(ref.1-3).ActivatedTGF-βtypeIreceptor(TβRI)andc-JunN-terminalkinase(JNK)differentiallyphosphorylateSmad3toconverttwodistinctivephosphoisoforms:C-terminallyphosphorylatedSmad3(pSmad3C)andlinker-phosphorylatedSmad3(pSmad3L)(ref.4).ReversIBLeshiftingofSmad-dependentsignalingbetweentumorsuppressionandoncogenesisinhyperactiveRas-expressingcellsindicatesthatpSmad3Ctransmitsatumor-suppressiveTGF-βsignalinmatureepithelialcells,whileoncogenicactivitiessuchascellproliferationandinvasionarepromotedbythepSmad3Lpathway(ref.5,6).Notably,pSmad3L-ediatedsignalinginactivatedmesenchymalcellspromotesfibrosisbystimulatingextracellularmatrixdeposition(ref.7,8).Asneoplasiaprogressesfromnormalepithelialcellsthroughadenomatocancer,thecellsundergotransitionfromthetumor-suppressivepSmad3Cpathway,whichischaracteristicofmatureepithelialcells,totheJNK/pSmad3Lpathway,whichappearstofavorthestateoffluxshownbytheactivatedmesenchymalcells(Fig.1,ref.9,10).Analysisofdomain-pecificphosphorylationstatesofSmad3withtheAbsshouldenhanceunderstandingofTGF-βsignalingincancerandfibrosis,andhelpmanyresearchersseekfornewtreatmentsofsuchdiseases.