线虫发育及基因功能研究2(韩珉)

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1、Pathwayinearly1992RASEGFRR7R8WTsevenlessR7receptorisrequiredforUVresponsesevBossStrategy:movingfromRTKdown:discoveringSOSRASGDPRASGTPPiGTPGDPGAPtargetproteinActivestateInactiveRTKSonofSevenless:hyperactivemutationRogerandBenejee,Cell1990Thestoryabout

2、RonRoger-+Sev/RTK(lf)SevenlessSev(lf)+SOS(gf)R7fineSevSOSR7fateLeadstoModel:A:yesB:maynot.Drosophila:F1screenvsF2screenX**X**F3homozygotesmutagenXTMTM**F1F2screenmutagenX**F1F1screenTMAconversationwithRubinMikeSimon:landmarkmodifyscreenSimonetal.1991

3、CellSevRASSOSR7Rougheye,noR7Mostlywt,small%defectsRougheyeRougheyeHighTLowTLowTLowTTsalleleX**F1F1screenTM+/-+/-SOSencodesanexchangefactorforGTPaseSimonetal.1991CellRASGDPRASGTPPiGTPGDPSOSGAPtargetproteinActivestateInactiveRTKMovingfromreceptordown:b

4、iochemistryRASGDPRASGTPPiGTPGDPGAPtargetproteinActivestateInactiveRTKSOSDiscoveryofGRB2EGFRYEGFRLigandactivationY-PScreenlGT11proteinexpressionlibrary9GRBproteinsWhichoneisonemediatedRasactivation?Y-PDiscoveryofGRB2:complementaryworksbybiochemistsand

5、geneticistsAcDNAcloneencodinganovel,widelyexpressedprotein(calledgrowthfactorreceptor-boundprotein2orGRB2)containingonesrchomology2(SH2)domainandtwoSH3domainswasisolated.ImmunoblottingexperimentsindicatethatGRB2associateswithtyrosine-phosphorylatedep

6、idermalgrowthfactorreceptors(EGFRs)andplatelet-derivedgrowthfactorreceptors(PDGFRs)viaitsSH2domain.Interestingly,GRB2exhibitsstrikingstructuralandfunctionalhomologytotheC.elegansproteinsem-5.Ithasbeenshownthatsem-5andtwoothergenescalledlet-23(EGFRlik

7、e)andlet-60(raslike)liealongthesamesignaltransductionpathwaycontrollingC.elegansvulvalinduction.ToexaminewhetherGRB2isalsoacomponentofrassignalinginmammaliancells,microinjectionstudieswereperformed.WhileinjectionofGRB2orH-rasproteinsaloneintoquiescen

8、tratfibroblastsdidnothavemitogeniceffect,microinjectionofGRB2togetherwithH-rasproteinstimulatedDNAsynthesis.TheseresultssuggestthatGRB2/sem-5playsacrucialroleinahighlyconservedmechanismforgrowthfactorcontrolofrassignaling.Lowensteinetal.Cell.Aug.1992