PTEN Negatively Regulates MAPK Signaling during Caenorhabditis elegans Vulval Development 英文参考文献.docVIP

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PTEN Negatively Regulates MAPK Signaling during Caenorhabditis elegans Vulval Development 英文参考文献.doc

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PTEN Negatively Regulates MAPK Signaling during Caenorhabditis elegans Vulval Development 英文参考文献

PTENNegativelyRegulatesMAPKSignalingduring CaenorhabditiselegansVulvalDevelopment ItayNakdimon1,2,MichaelWalser1,3,ErikaFro¨hli1,AlexHajnal1* 1InstituteofMolecularLifeSciences,UniversityofZu¨rich,Zu¨rich,Switzerland,2CancerNetworkZu¨richPhDProgram,InstituteofMolecularLifeSciences,Universityof Zu¨rich,Zu¨rich,Switzerland,3MolecularLifeSciencesPhDProgram,InstituteofMolecularLifeSciences,UniversityofZu¨rich,Zu¨rich,Switzerland Abstract Vulval development in Caenorhabditis elegans serves as an excellent model to examine the crosstalk between different conservedsignalingpathwaysthatarederegulatedinhumancancer.TheconcertedactionoftheRAS/MAPK,NOTCH,and WNTpathwaysdeterminesaninvariantpatternofcellfatesinthreevulvalprecursorcells.Wehavediscoveredanovelform ofcrosstalkbetweencomponentsoftheInsulinandtheRAS/MAPKpathways.TheinsulinreceptorDAF-2stimulates,while DAF-18PTENinhibits,RAS/MAPKsignalinginthevulvalprecursorcells.Surprisingly,theinhibitoryactivityofDAF-18PTEN on the RAS/MAPK pathway is partially independent of its PIP3 lipid phosphatase activity and does not involve further downstreamcomponentsoftheinsulinpathway,suchasAKTandDAF-16FOXO.Geneticandbiochemicalanalysesindicate that DAF-18 negatively regulates vulval induction by inhibiting MAPK activation. Thus, mutations in the PTEN tumor suppressorgenemayresultinthesimultaneoushyper-activationoftwooncogenicsignalingpathways. Citation:NakdimonI,WalserM,Fro¨hliE,HajnalA(2012)PTENNegativelyRegulatesMAPKSignalingduringCaenorhabditiselegansVulvalDevelopment.PLoS Genet8(8):e1002881.doi:10.1371/journal.pgen.1002881 Editor:StuartK.Kim,StanfordUniversityMedicalCenter,UnitedStatesofAmerica ReceivedFebruary3,2012;AcceptedJune19,2012;PublishedAugust16,2012 Copyright: ?2012 Nakdimon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:Thisworkwassuppor