Keeping the Receptor Tyrosine Kinase Signaling Pathway in Check: Lessons from Drosophila

Developmental Biology

Ilaria Rebay¹ 

[1] Whitehead Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142

关键词: receptor tyrosine kinase;    Ras;    MAPK;    signal transduction;    feedback regulation;    Drosophila;   

DOI  :  10.1006/dbio.2002.0806

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Thereceptortyrosinekinase(RTK)signalingnetworkplaysacentralroleinregulatingcellulardifferentiation,proliferation,andsurvivalinallmetazoananimals.ExcessiveorcontinuousactivationoftheRTKpathwayhasbeenlinkedtocarcinogenesisinmammals,underscoringtheimportanceofpreventinguncontrolledsignaling.ThisreviewwillfocusontheinhibitorymechanismsthatkeepRTK-mediatedsignalsincheck,withemphasisonconservedprinciplesdiscernedfromstudiesusingDrosophilaasamodelsystem.Twogeneralstrategiesofinhibitionwillbediscussed.Thefirst,thresholdregulation,postulatesthataneffectivewayofantagonizingRTKsignalingistoerectandmaintainhighthresholdbarriersthatpreventinappropriateresponsestomoderatesignalinglevels.Activationofthepathwayabovethislevelovercomestheinhibitoryblocksandshiftsthebalancetoallowapositiveflowofinductiveinformation.Asecondlayerofnegativeregulationinvolvinginductionofnegativefeedbackloopsthatlimittheextent,strength,ordurationofthesignalpreventsrunawaysignalinginresponsetothehighlevelsofactivationrequiredtosurmountthethresholdbarriers.Suchautoinhibitorymechanismsattenuatesignalingatcriticalpointsthroughoutthenetwork,fromthereceptortothedownstreameffectors.

【 授权许可】

Unknown