Keeping the Receptor Tyrosine Kinase Signaling Pathway in Check: Lessons from Drosophila
[摘要] Thereceptortyrosinekinase(RTK)signalingnetworkplaysacentralroleinregulatingcellulardifferentiation,proliferation,andsurvivalinallmetazoananimals.ExcessiveorcontinuousactivationoftheRTKpathwayhasbeenlinkedtocarcinogenesisinmammals,underscoringtheimportanceofpreventinguncontrolledsignaling.ThisreviewwillfocusontheinhibitorymechanismsthatkeepRTK-mediatedsignalsincheck,withemphasisonconservedprinciplesdiscernedfromstudiesusingDrosophilaasamodelsystem.Twogeneralstrategiesofinhibitionwillbediscussed.Thefirst,thresholdregulation,postulatesthataneffectivewayofantagonizingRTKsignalingistoerectandmaintainhighthresholdbarriersthatpreventinappropriateresponsestomoderatesignalinglevels.Activationofthepathwayabovethislevelovercomestheinhibitoryblocksandshiftsthebalancetoallowapositiveflowofinductiveinformation.Asecondlayerofnegativeregulationinvolvinginductionofnegativefeedbackloopsthatlimittheextent,strength,ordurationofthesignalpreventsrunawaysignalinginresponsetothehighlevelsofactivationrequiredtosurmountthethresholdbarriers.Suchautoinhibitorymechanismsattenuatesignalingatcriticalpointsthroughoutthenetwork,fromthereceptortothedownstreameffectors.
[发布日期] [发布机构]
[效力级别] [学科分类] 生物科学（综合）
[关键词] receptor tyrosine kinase;Ras;MAPK;signal transduction;feedback regulation;Drosophila [时效性]
