ArticleThe Journal of biological chemistry2010
Systematic quantification of negative feedback mechanisms in the extracellular signal-regulated kinase (ERK) signaling network.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 85 citations in OpenAlex.
- A single mechanism can explain network-wide insulin resistance in adipocytes from obese patients with type 2 diabetes.The Journal of biological chemistry · 2014Trial
- Optogenetics with Atomic Precision─A Comprehensive Review of Optical Control of Protein Function through Genetic Code Expansion.Chemical reviews · 2025Review
- A guide to ERK dynamics, part 1: mechanisms and models.The Biochemical journal · 2023Article
- Targeted Quantification of Protein Phosphorylation and Its Contributions towards Mathematical Modeling of Signaling Pathways.Molecules (Basel, Switzerland) · 2023Review
- Relating individual cell division events to single-cell ERK and Akt activity time courses.Scientific reports · 2022Article
- Regulation of the Small GTPase Ras and Its Relevance to Human Disease.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Signaling Pathways in Proton and Non-proton ASIC1a Activation.Frontiers in cellular neuroscience · 2021Article
- Adhesion-growth factor crosstalk regulates AURKB activation and ERK signalling in re-adherent fibroblasts.Journal of biosciences · 2021Article
- Kinetics of receptor tyrosine kinase activation define ERK signaling dynamics.Science signaling · 2020Article
- Evaluation of the profiles of CBBritish journal of pharmacology · 2020Article
- The road to ERK activation: Do neurons take alternate routes?Cellular signalling · 2020Review
- Inferring Leading Interactions in the p53/Mdm2/Mdmx Circuit through Live-Cell Imaging and Modeling.Cell systems · 2019Article
- Article
- Importance of Feedback and Feedforward Loops to Adaptive Immune Response Modeling.CPT: pharmacometrics & systems pharmacology · 2018Review
- Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine.Nature communications · 2018Article
- Optochemical Control of Biological Processes in Cells and Animals.Angewandte Chemie (International ed. in English) · 2018Review
- KRAS mutant allele-specific expression knockdown in pancreatic cancer model with systemically delivered bi-shRNA KRAS lipoplex.PloS one · 2018Article
- PTEN loss and activation of K-RAS and β-catenin cooperate to accelerate prostate tumourigenesis.The Journal of pathology · 2017Article
- Mechanisms and causality in molecular diseases.History and philosophy of the life sciences · 2017Review
- Kinetic Modeling and Analysis of the Akt/Mechanistic Target of Rapamycin Complex 1 (mTORC1) Signaling Axis Reveals Cooperative, Feedforward Regulation.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cell responses are actuated by tightly controlled signal transduction pathways. Although the concept of an integrated signaling network replete with interpathway cross-talk and feedback regulation is broadly appreciated, kinetic data of the type needed to characterize such interactions in conjunction with mathematical models are lacking. In mammalian cells, the Ras/ERK pathway controls cell proliferation and other responses stimulated by growth factors, and several cross-talk and feedback mechanisms affecting its activation have been identified. In this work, we take a systematic approach to parse the magnitudes of multiple regulatory mechanisms that attenuate ERK activation through canonical (Ras-dependent) and non-canonical (PI3K-dependent) pathways. In addition to regulation of receptor and ligand levels, we consider three layers of ERK-dependent feedback: desensitization of Ras activation, negative regulation of MEK kinase (e.g. Raf) activities, and up-regulation of dual-specificity ERK phosphatases. Our results establish the second of these as the dominant mode of ERK self-regulation in mouse fibroblasts. We further demonstrate that kinetic models of signaling networks, trained on a sufficient diversity of quantitative data, can be reasonably comprehensive, accurate, and predictive in the dynamical sense.
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Registered trials
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.