Alphabet, a Ser/Thr phosphatase of the protein phosphatase 2C family, negatively regulates RAS/MAPK signaling in Drosophila

摘要

SignaltransductionthroughtheRAS/mitogen-activatedproteinkinase(MAPK)pathwaydependsonadiversecollectionofproteinsregulatingpositivelyandnegativelysignalingflow.WepreviouslyconductedageneticscreeninemDrosophila/emtoidentifynovelcomponentsofthissignalingpathway.Here,wepresenttheidentificationandcharacterizationofanewgene,emalphabet/em(emalph/em),whoseactivitynegativelyregulatesRAS/MAPK-dependentdevelopmentalprocessesinemDrosophila/emandthis,atastepdownstreamorinparalleltoRAS.emalph/emencodesaproteinphosphatase2C(PP2C)familymembercloselyrelatedtothemammalianPP2Calphaandbetaisoforms.Interestingly,althoughemalph/emgeneproductdoesnotappeartobeessentialforviability,itseliminationleadstoweakbutsignificantdevelopmentaldefectsreminiscentofanoveractivatedRAS/MAPKpathway.Consistentwiththisinterpretation,stronggeneticinteractionsareobservedbetweenemalph/emallelesandmutationsinbonafidecomponentsofthepathway.Together,thisworkidentifiesaPP2Cofthealpha/betasubfamilyasanovelnegativeregulatoroftheRAS/MAPKpathwayandsuggeststhattheseevolutionarilyconservedenzymesplayasimilarroleinothermetazoans.Finally,despitetherelativelylargesizeoftheemPP2C/emgenefamilyinmetazoans,thisstudyrepresentsonlythesecondgeneticcharacterizationofaPP2Cintheseorganisms./p/div