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dc.contributor.authorFletcher, PA
dc.contributor.authorClément, F
dc.contributor.authorVidal, A
dc.contributor.authorTabak, J
dc.contributor.authorBertram, R
dc.date.accessioned2016-04-11T08:12:45Z
dc.date.issued2014-04-18
dc.description.abstractMany hormones are released in pulsatile patterns. This pattern can be modified, for instance by changing pulse frequency, to encode relevant physiological information. Often other properties of the pulse pattern will also change with frequency. How do signaling pathways of cells targeted by these hormones respond to different input patterns? In this study, we examine how a given dose of hormone can induce different outputs from the target system, depending on how this dose is distributed in time. We use simple mathematical models of feedforward signaling motifs to understand how the properties of the target system give rise to preferences in input pulse pattern. We frame these problems in terms of frequency responses to pulsatile inputs, where the amplitude or duration of the pulses is varied along with frequency to conserve input dose. We find that the form of the nonlinearity in the steady state input-output function of the system predicts the optimal input pattern. It does so by selecting an optimal input signal amplitude. Our results predict the behavior of common signaling motifs such as receptor binding with dimerization, and protein phosphorylation. The findings have implications for experiments aimed at studying the frequency response to pulsatile inputs, as well as for understanding how pulsatile patterns drive biological responses via feedforward signaling pathways.en_GB
dc.description.sponsorshipThis work was partially supported by the National Science Foundation grant DMS-1220063 to R. Bertram and J. Tabak (http://www.nsf.gov) and by the large-scale action REGATE (REgulation of the GonAdoTropE axis) to F. Clement and A. Vidal (https://www.rocq.inria.fr/sisyphe/reglo/regate.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_GB
dc.identifier.citationPLoS One, 2014, Vol. 9 (4): e95613en_GB
dc.identifier.doi10.1371/journal.pone.0095613
dc.identifier.urihttp://hdl.handle.net/10871/21028
dc.language.isoenen_GB
dc.publisherPublic Library of Scienceen_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/24748217en_GB
dc.subjectActivity Cyclesen_GB
dc.subjectAlgorithmsen_GB
dc.subjectCell Communicationen_GB
dc.subjectHormonesen_GB
dc.subjectHumansen_GB
dc.subjectKineticsen_GB
dc.subjectLigandsen_GB
dc.subjectModels, Biologicalen_GB
dc.subjectPhosphorylationen_GB
dc.subjectProtein Bindingen_GB
dc.subjectProtein Multimerizationen_GB
dc.subjectReceptors, Cell Surfaceen_GB
dc.subjectSignal Transductionen_GB
dc.titleInterpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs.en_GB
dc.typeArticleen_GB
dc.date.available2016-04-11T08:12:45Z
dc.identifier.issn1932-6203
exeter.place-of-publicationUnited States
dc.descriptionThis is the final version of the article. Available from PLoS via the DOI in this record.en_GB
dc.identifier.journalPLoS Oneen_GB


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