Seeonlineversionforlegend,abbreviations,andreferences.1204Cell131,December14,2007©2007ElsevierInc.DOI10.1016/j.cell.2007.11.036SnapShot:Wnt/β-CateninSignalingBryanT.MacDonald,MikhailV.Semenov,andXiHeTheF.M.KirbyNeurobiologyCenter,Children’sHospitalBoston,HarvardMedicalSchool,Boston,MA02115,USASnapShot:Wnt/β-CateninSignalingBryanT.MacDonald,MikhailV.Semenov,andXiHeTheF.M.KirbyNeurobiologyCenter,Children’sHospitalBoston,HarvardMedicalSchool,Boston,MA02115,USA1204.e1Cell131,December14,2007©2007ElsevierInc.DOI10.1016/j.cell.2007.11.036MoleculeslabeledingreenandblueplaypositiveandnegativerolesinWnt/β-cateninsignaling,respectively.Moleculesthatarelabeledinbothcolorshavedualroles.(Topleft)Wntbiogenesis.AlipidmodificationisaddedtoWntligandsbyPorcintheendoplasmicreticulum(ER).WntligandsareglycosylatedintheERandGolgiandrequireWls(alsoknownasEvi)totrafficthroughtheGolgitotheplasmamembrane.TheretromercomplexisalsoimportantforWntsecretion,particularlyforlong-rangesignaling.MatureWntligandsmayinteractwithlipoproteinparticles.ProteoglycansDallyandKny/GlypicanmayalsofacilitateWntdistribution.(Bottomright)Wntreceptorbiogenesis.IncellsthatrespondtoWnttheERproteinMESDisrequiredforfoldingandtraffickingoftheWntreceptorLRP5/6totheplasmamembrane,andtheERproteinShisapreventsfoldingandtraffickingoftheFzproteintotheplasmamembrane.(Right)Wnt/β-cateninsignalingOFF.sFRPandWIF1directlybindWntligandsandpreventWntsfrombindingtoreceptors.SOST/WISE,CTGF/Cyr61bindtoLRP6(CTGFmayalsobindtoFz)topreventtheformationoftheWnt-Fz-LRP5/6receptorcomplex.DKKbindstoandinhibitsLRP5/6incooperationwiththeKRMreceptor.IntheabsenceofWntsignaling,thescaffoldingproteinAxinandtumorsuppressorAPCformaβ-catenindestructioncomplexthatbindscytosolicβ-cateninandfacilitatessequentialphos-phorylationofβ-cateninbyCK1(atS45)andGSK3(atS33/S37/T41).ThetumorsuppressorWTXmayalsoresideinthiscomplex.Phosphorylatedβ-cateninisrecognizedbyβ-Trcpandubiquitinatedfordegradationbytheproteasome.Inthenucleus,TCFassemblesatranscrip...
