Spatial Regulation and the Rate of Signal Transduction Activation 英文参考文献.docVIP

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Spatial Regulation and the Rate of Signal Transduction Activation 英文参考文献.doc

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Spatial Regulation and the Rate of Signal Transduction Activation 英文参考文献

SpatialRegulationandtheRateofSignal TransductionActivation Nizar N.Batada1¤*,Larry A.Shepp2,David O.Siegmund3,Michael Levitt4 1PrograminBiophysics,StanfordUniversity,Stanford,California,UnitedStatesofAmerica,2DepartmentofStatistics,RutgersUniversity,Piscataway,NewJersey,United States ofAmerica, 3 Department of Statistics, StanfordUniversity,Stanford, California, United States ofAmerica, 4Department ofStructural Biology, Stanford School of Medicine,Stanford,California,UnitedStatesofAmerica Of the many important signaling events that take place on the surface of a mammalian cell, activation of signal transductionpathwaysviainteractionsofcellsurfacereceptorsisoneofthemostimportant.Evidencesuggeststhat cellsurfaceproteinsarenotasfreelydiffusibleasimpliedbytheclassicfluidmosaicmodelandthattheirconfinement tomembranedomainsisregulated.Itisunknownwhetherthesedynamiclocalizationmechanismsfunctiontoenhance signaltransductionactivationrateortominimizecrosstalkamongpathwaysthatsharecommonintermediates.To determine which of these two possibilities is more likely, we derive an explicit equation for the rate at which cell surfacemembraneproteinsinteractbasedonaBrownianmotionmodelinthepresenceofendocytosisandexocytosis. Wefindthatintheabsenceofanydiffusionconstraints,cellsurfaceproteininteractionrateisextremelyhighrelative to cytoplasmic protein interaction rate even in a large mammalian cell with a receptor abundance of a mere two hundredmolecules.Sincealargernumberofdownstreamsignalingeventsneedstotakeplace,eachoccurringata muchslowerratethantheinitialactivation viaassociationofcellsurfaceproteins,weconclude thattheroleofco- localizationismostlikelythatofcross-talkreductionratherthancouplingefficiencyenhancement. Citation:BatadaNN,SheppLA,SiegmundDO,LevittM(2006)Spatialregulationandtherateofsignaltransductionactivation.PLoSComputBiol2(5):e44. DOI:10.1371/journal.pcbi.0020044 proteins causing anomalous diffusion [11,12]. In addition, cellscantransientlycon?nemembranep