ArticleProceedings of the National Academy of Sciences of the United States of America2014
Information transfer by leaky, heterogeneous, protein kinase signaling systems.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- Uncovering the molecular basis of kinase activity and substrate recognition with phospho-PCA.bioRxiv : the preprint server for biology · 2025Article
- Limits on the computational expressivity of non-equilibrium biophysical processes.Nature communications · 2025Article
- Individual yeast cells signal at different levels but each with good precision.Royal Society open science · 2025Article
- Non-Equilibrium Enhancement of Classical Information Transmission.Entropy (Basel, Switzerland) · 2024Article
- Improved approaches to channel capacity estimation discover compromised GPCR signaling in diverse cancer cells.iScience · 2023Article
- An optimized reporter of the transcription factor hypoxia-inducible factor 1α reveals complex HIF-1α activation dynamics in single cells.The Journal of biological chemistry · 2023Article
- Efficient information coding and degeneracy in the nervous system.Current opinion in neurobiology · 2022Review
- Quantifying information of intracellular signaling: progress with machine learning.Reports on progress in physics. Physical Society (Great Britain) · 2022Review
- Mathematical models in GnRH research.Journal of neuroendocrinology · 2022Review
- Mapping the dynamic transfer functions of eukaryotic gene regulation.Cell systems · 2021Article
- The tyrosine phosphatase SHP2 increases robustness and information transfer within IL-6-induced JAK/STAT signalling.Cell communication and signaling : CCS · 2021Article
- Article
- Quantifying information accumulation encoded in the dynamics of biochemical signaling.Nature communications · 2021Article
- Promoters adopt distinct dynamic manifestations depending on transcription factor context.Molecular systems biology · 2021Article
- Information transmission from NFkB signaling dynamics to gene expression.PLoS computational biology · 2020Article
- First-principles prediction of the information processing capacity of a simple genetic circuit.Physical review. E · 2020Article
- Multiplexing information flow through dynamic signalling systems.PLoS computational biology · 2020Article
- Design of a MAPK signalling cascade balances energetic cost versus accuracy of information transmission.Nature communications · 2020Article
- The effects of proliferation status and cell cycle phase on the responses of single cells to chemotherapy.Molecular biology of the cell · 2020Article
- Heterogeneities in intrinsic excitability and frequency-dependent response properties of granule cells across the blades of the rat dentate gyrus.Journal of neurophysiology · 2020Article
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5 authors.
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Abstract
Cells must sense extracellular signals and transfer the information contained about their environment reliably to make appropriate decisions. To perform these tasks, cells use signal transduction networks that are subject to various sources of noise. Here, we study the effects on information transfer of two particular types of noise: basal (leaky) network activity and cell-to-cell variability in the componentry of the network. Basal activity is the propensity for activation of the network output in the absence of the signal of interest. We show, using theoretical models of protein kinase signaling, that the combined effect of the two types of noise makes information transfer by such networks highly vulnerable to the loss of negative feedback. In an experimental study of ERK signaling by single cells with heterogeneous ERK expression levels, we verify our theoretical prediction: In the presence of basal network activity, negative feedback substantially increases information transfer to the nucleus by both preventing a near-flat average response curve and reducing sensitivity to variation in substrate expression levels. The interplay between basal network activity, heterogeneity in network componentry, and feedback is thus critical for the effectiveness of protein kinase signaling. Basal activity is widespread in signaling systems under physiological conditions, has phenotypic consequences, and is often raised in disease. Our results reveal an important role for negative feedback mechanisms in protecting the information transfer function of saturable, heterogeneous cell signaling systems from basal activity.
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