ArticlePloS one2014
Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 25 citations in OpenAlex.
- The advantage of periodic over constant signalling in microRNA-mediated regulation.Nucleic acids research · 2025Article
- Transient frequency preference responses in cell signaling systems.NPJ systems biology and applications · 2024Article
- Network motifs exhibiting a differential response to spaced and massed inputs.Learning & memory (Cold Spring Harbor, N.Y.) · 2024Article
- Article
- Mathematical models in GnRH research.Journal of neuroendocrinology · 2022Review
- A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance.Nature communications · 2017Article
- Mathematical modeling of gonadotropin-releasing hormone signaling.Molecular and cellular endocrinology · 2017Review
- Modeling and high-throughput experimental data uncover the mechanisms underlyingThe Journal of biological chemistry · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many 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.
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Registered trials
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