Enzyme Localization Can Drastically Affect Signal Amplification in Signal Transduction Pathways 英文参考文献.docVIP

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Enzyme Localization Can Drastically Affect Signal Amplification in Signal Transduction Pathways 英文参考文献.doc

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Enzyme Localization Can Drastically Affect Signal Amplification in Signal Transduction Pathways 英文参考文献

EnzymeLocalizationCanDrasticallyAffect SignalAmplificationinSignalTransduction Pathways Siebe B.van Albada, Pieter Rein ten Wolde* FOMInstituteforAtomicandMolecularPhysics,Amsterdam,TheNetherlands Push–pullnetworksareubiquitousinsignaltransductionpathwaysinbothprokaryoticandeukaryoticcells.Theyallow cellstostronglyamplifysignalsviathemechanismofzero-orderultrasensitivity.Inapush–pullnetwork,twoantagonistic enzymescontroltheactivityofaproteinbycovalentmodification.Theseenzymesareoftenuniformlydistributedinthe cytoplasm. They can, however, also be colocalized in space; for instance, near the pole of the cell. Moreover, it is increasinglyrecognizedthattheseenzymescanalsobespatiallyseparated,leadingtogradientsoftheactiveformofthe messenger protein. Here, we investigate the consequences of the spatial distributions of the enzymes for the amplificationpropertiesofpush–pullnetworks.Ourcalculationsrevealthatenzymelocalizationbyitselfcanhavea dramaticeffectonthegain.Thegainismaximizedwhenthetwoenzymesareeitheruniformlydistributedorcolocalized inoneregioninthecell.Dependingonthediffusionconstants,however,thesharpnessoftheresponsecanbestrongly reducedwhentheenzymesarespatiallyseparated.Wediscusshowourpredictionscouldbetestedexperimentally. Citation:vanAlbadaSB,tenWoldePR(2007)Enzymelocalizationcandrasticallyaffectsignalamplificationinsignaltransductionpathways.PLoSComputBiol3(10):e195. doi:10.1371/journal.pcbi.0030195 Escherichiacolicells,thekinaseCheAandthephosphataseCheZ control the phosphorylation level of the messenger CheY, Introduction Living cells are information processing machines. To process information reliably, signals often need to be ampli?ed. To this end, cells can employ a variety of ampli?cation mechanisms. Signals can be ampli?ed via positivefeedback,cooperativebindingofsignalingmolecules toreceptors,orinteractionsbetweenreceptormolecules[1]. Anotherprincipalmechanismforsignalampli?cationiszero- order ultrasensitivity [2,3]. This mechanism operates in