Differential Palmit(e)oylation of Wnt1 on C93 and S224 Residues Has Overlapping and Distinct Consequences 英文参考文献.docVIP

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Differential Palmit(e)oylation of Wnt1 on C93 and S224 Residues Has Overlapping and Distinct Consequences 英文参考文献.doc

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Differential Palmit(e)oylation of Wnt1 on C93 and S224 Residues Has Overlapping and Distinct Consequences 英文参考文献

DifferentialPalmit(e)oylationofWnt1onC93andS224 ResiduesHasOverlappingandDistinctConsequences LisaM.Galli,LauraW.Burrus* DepartmentofBiology,SanFranciscoStateUniversity,SanFrancisco,California,UnitedStatesofAmerica Abstract Though the mechanisms by which cytosolic/intracellular proteins are regulated by the post-translational addition of palmitate adducts is well understood, little is known about how this lipid modification affects secreted ligands, such as Wnts.Hereweusemutationalanalysistoshowthatdifferentialmodificationofthetwoknownpalmit(e)oylatedresiduesof Wnt1,C93andS224,hasbothoverlappinganddistinctconsequences.Thoughtherelativerolesofeachresiduearesimilar with respect to stability and secretion, two distinct biological assays in L cells show that modification of C93 primarily modulates signaling via a ?-catenin independent pathway while S224 is crucial for ?-catenin dependent signaling. In addition,pharmacologicalinhibitionofPorcupine(Porcn),anupstreamregulatorofWnt,byIWP1,specificallyinhibited?- catenindependentsignaling.Consistentwiththeseobservations,mappingofaminoacidsinpeptidedomainscontaining C93andS224demonstratethatacylationofC93islikelytobePorcn-independentwhilethatofS224isPorcn-dependent. Cumulatively, our data strongly suggest that C93 and S224 are modified by distinct enzymes and that the differential modificationofthesesiteshasthepotentialtoinfluenceWntsignalingpathwaychoice. Citation: Galli LM, Burrus LW (2011) Differential Palmit(e)oylation of Wnt1 on C93 and S224 Residues Has Overlapping and Distinct Consequences. PLoS ONE6(10):e26636.doi:10.1371/journal.pone.0026636 Editor:Karl-WilhelmKoch,UniversityofOldenburg,Germany ReceivedMay11,2011;AcceptedSeptember30,2011;PublishedOctober26,2011 Copyright: ? 2011 Galli, Burrus. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Fund