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The role of stochastic sequestration dynamics for intrinsic noise filtering in signaling network motifs
Open accessPublished version of a preprint
Abstract
The relation between design principles of signaling network motifs and their robustness against intrinsic noise still remains illusive. In this work we investigate the role of cascading for coping with intrinsic noise due to stochasticity in molecular reactions. We use stochastic approaches to quantify fluctuations in the terminal kinase of phosphorylation-dephosphorylation cascade motifs and demonstrate that cascading highly affects these fluctuations. We show that this purely stochastic effect can be explained by time-varying sequestration of upstream kinase molecules. In particular, we discuss conditions on time scales and parameter regimes which lead to a reduction of output fluctuations. Our results are put into biological context by adapting rate parameters of our modeling approach to biologically feasible ranges for general binding-unbinding and phosphorylation-dephosphorylation mechanisms. Overall, this study reveals a novel role of stochastic sequestration for dynamic noise filtering in signaling cascade motifs.
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Self-citation
Research works printed but not linked: 1
- Kim, 2011, Substrate-dependent control of MAPK phosphorylation in vivo, Mol. Syst. Biol., 467
Metadata
- Authors
- Paul, D., & Radde, N.
- Affiliations
- University of Stuttgart (DE)
- Corresponding author
- Paul, Debdas
- Venue
- Journal of Theoretical Biology
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 455
- Pages
- 86-96
- ISSN
- 0022-5193 (ISSN-L)
- OpenAlex
- W2951132898
- Cited by
- 1
- References
- 33
- Citations by year
- 2019: 1
- FWCI
- 0.09
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- Locations
- Journal of Theoretical Biology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft ((EXC 310/2), EXC 310)
- Universität Stuttgart (EXC 310/2)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › Advanced Thermodynamics and Statistical Mechanics
- Keywords
- intrinsic noise, noise reduction, cascading, time scales, molecular fluctuations
- MeSH terms
- Animals, Computer Simulation, Humans, Models, Biological, Phosphorylation, Phosphotransferases, Stochastic Processes, Signal Transduction
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