ArticleBiophysical journal2018
When More Is Less: Dual Phosphorylation Protects Signaling Off State against Overexpression.
Article in Biophysical journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed, 4 citations in OpenAlex.
- EMBED: Ensemble MATCONT-Based Detection and Classification of Bifurcations in Dual Phosphorylation-Dephosphorylation Reaction Networks.ACS omega · 2026Article
- Article
- Network regulation meets substrate modification chemistry.Journal of the Royal Society, Interface · 2023Article
- Exploring cyclic networks of multisite modification reveals origins of information processing characteristics.Scientific reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kinases in signaling pathways are commonly activated by multisite phosphorylation. For example, the mitogen-activated protein kinase Erk is activated by its kinase Mek by two consecutive phosphorylations within its activation loop. In this article, we use kinetic models to study how the activation of Erk is coupled to its abundance. Intuitively, Erk activity should rise with increasing amounts of Erk protein. However, a mathematical model shows that the signaling off state is robust to increasing amounts of Erk, and Erk activity may even decline with increasing amounts of Erk. This counterintuitive, bell-shaped response of Erk activity to increasing amounts of Erk arises from the competition of the unmodified and single phosphorylated form of Erk for access to its kinase Mek. This shows that phosphorylation cycles can contain an intrinsic robustness mechanism that protects signaling from aberrant activation e.g., by gene expression noise or kinase overexpression after gene duplication events in diseases like cancer.
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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.