ArticleBiophysical journal2011
Long signaling cascades tend to attenuate retroactivity.
Article in Biophysical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 1 citations in OpenAlex.
- Dynamics and Sensitivity of Signaling Pathways.Current pathobiology reports · 2022Article
- What Is the Trait d'Union between Retroactivity and Molecular Communication Performance Limits?Molecules (Basel, Switzerland) · 2022Article
- Frequency-preference response in covalent modification cycles under substrate sequestration conditions.NPJ systems biology and applications · 2021Article
- Article
- Exploring the intrinsic behaviour of multisite phosphorylation systems as part of signalling pathways.Journal of the Royal Society, Interface · 2018Article
- Beyond the Michaelis-Menten equation: Accurate and efficient estimation of enzyme kinetic parameters.Scientific reports · 2017Article
- Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity.Biophysical journal · 2017Article
- Dynamics robustness of cascading systems.PLoS computational biology · 2017Article
- Modular bond-graph modelling and analysis of biomolecular systems.IET systems biology · 2016Article
- Signaling cascades transmit information downstream and upstream but unlikely simultaneously.BMC systems biology · 2016Article
- Quantification of Interactions between Dynamic Cellular Network Functionalities by Cascaded Layering.PLoS computational biology · 2015Article
- Retroactivity in the Context of Modularly Structured Biomolecular Systems.Frontiers in bioengineering and biotechnology · 2015Review
- The energy costs of insulators in biochemical networks.Biophysical journal · 2013Article
- A generic model for open signaling cascades with forward activation.Journal of mathematical biology · 2012Article
- Article
- Retroactive signaling in short signaling pathways.PloS one · 2012Article
- Kinase inhibitors can produce off-target effects and activate linked pathways by retroactivity.BMC systems biology · 2011Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling pathways consisting of phosphorylation/dephosphorylation cycles with no explicit feedback allow signals to propagate not only from upstream to downstream but also from downstream to upstream due to retroactivity at the interconnection between phosphorylation/dephosphorylation cycles. However, the extent to which a downstream perturbation can propagate upstream in a signaling cascade and the parameters that affect this propagation are presently unknown. Here, we determine the downstream-to-upstream steady-state gain at each stage of the signaling cascade as a function of the cascade parameters. This gain can be made smaller than 1 (attenuation) by sufficiently fast kinase rates compared to the phosphatase rates and/or by sufficiently large Michaelis-Menten constants and sufficiently low amounts of total stage protein. Numerical studies performed on sets of biologically relevant parameters indicated that ∼50% of these parameters could give rise to amplification of the downstream perturbation at some stage in a three-stage cascade. In an n-stage cascade, the percentage of parameters that lead to an overall attenuation from the last stage to the first stage monotonically increases with the cascade length n and reaches 100% for cascades of length at least 6.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.