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Positional Information Generated by Spatially Distributed Signaling Cascades 英文参考文献
PositionalInformationGeneratedbySpatially
DistributedSignalingCascades
JavierMun?oz-Garc?′a1,2,ZoltanNeufeld1,BorisN.Kholodenko3,4*
1SchoolofMathematicalSciencesandComplexAdaptiveSystemsLaboratory,UniversityCollegeDublin,Dublin,Ireland,2GrupoInterdisciplinardeSistemasComplejos
(GISC), Madrid, Spain, 3UCD Conway Institute, University College Dublin, Dublin, Ireland, 4Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson
University,Philadelphia,Pennsylvania,UnitedStatesofAmerica
Abstract
The temporal and stationary behavior of protein modification cascades has been extensively studied, yet little is known
aboutthespatialaspectsofsignalpropagation.Wehavepreviouslyshownthatthespatialseparationofopposingenzymes,
suchasakinaseandaphosphatase,createssignalingactivitygradients.Hereweshowunderwhatconditionssignalsstallin
the space or robustly propagate through spatially distributed signaling cascades. Robust signal propagation results in
activity gradients with long plateaus, which abruptly decay at successive spatial locations. We derive an approximate
analyticalsolutionthatrelatesthemaximalamplitudeandpropagationlengthofeachactivationprofilewiththecascade
level, protein diffusivity, and the ratio of the opposing enzyme activities. The control of the spatial signal propagation
appears to be very different from the control of transient temporal responses for spatially homogenous cascades. For
spatially distributed cascades where activating and deactivating enzymes operate far from saturation, the ratio of the
opposing enzyme activities is shown to be a key parameter controlling signal propagation. The signaling gradients
characteristic for robust signal propagation exemplify a pattern formation mechanism that generates precise spatial
guidanceformultiplecellularprocessesandconveysinformationaboutthecellsizetothenucleus.
Citation:Mun?oz-Garc?′aJ,NeufeldZ,KholodenkoBN(2009)PositionalInformationGeneratedbySpatiallyDistributedSignalingCascades.PLoSComputBiol5(3):
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