ArticlePLoS computational biology2017
An Asymmetrically Balanced Organization of Kinases versus Phosphatases across Eukaryotes Determines Their Distinct Impacts.
Article in PLoS computational biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
26 citing papers in PubMed, 48 citations in OpenAlex.
- Phosphoproteomic dysregulation promotes tumor proliferation in Cushing's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Anti-inflammatory and phosphorylation effects of CFTR modulator triple therapy in cystic fibrosis.iScience · 2026Article
- Type one protein phosphatases (TOPPs) catalyze EIN2 dephosphorylation to regulate ethylene signaling inScience advances · 2026Article
- Human clearance systems have a layered architecture across tissues and cell types that supports varied proteome compositions.Autophagy · 2026Article
- Expression, Purification, and Preliminary Characterization of Putative Protein Tyrosine Phosphatase Oca1.Protein and peptide letters · 2025Article
- Genome-wide identification, phylogenetic investigation and abiotic stress responses analysis of theFrontiers in plant science · 2025Article
- A highly efficient catalytic method for the synthesis of phosphite diesters.Chemical science · 2024Article
- Interaction networks explain holoenzyme allostery in Protein Kinase A.Kinases and phosphatases · 2023Article
- Key role of phosphorylation sites in ATPase domain and Linker region of MLH1 for DNA binding and functionality of MutLα.Scientific reports · 2023Article
- Phosphorylation of the PA subunit of influenza polymerase at Y393 prevents binding of the 5'-termini of RNA and polymerase function.Scientific reports · 2023Article
- Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules.The Journal of biological chemistry · 2022Review
- Review
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- Photoactivatable Reporter to Perform Multiplexed and Temporally Controlled Measurements of Kinase and Protease Activity in Single Cells.Analytical chemistry · 2021Article
- A phosphatase-centric mechanism drives stress signaling response.EMBO reports · 2021Article
- Growth Promotion or Osmotic Stress Response: How SNF1-Related Protein Kinase 2 (SnRK2) Kinases Are Activated and Manage Intracellular Signaling in Plants.Plants (Basel, Switzerland) · 2021Review
- Protein phosphatases in the RNAPII transcription cycle: erasers, sculptors, gatekeepers, and potential drug targets.Genes & development · 2021Review
- Phospho-Regulation of Meiotic Prophase.Frontiers in cell and developmental biology · 2021Review
- Cardiac Troponin T: The Impact of Posttranslational Modifications on Analytical Immunoreactivity in Blood up to the Excretion in Urine.Advances in experimental medicine and biology · 2021Article
- Asymmetry between Activators and Deactivators in Functional Protein Networks.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
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein phosphorylation underlies cellular response pathways across eukaryotes and is governed by the opposing actions of phosphorylating kinases and de-phosphorylating phosphatases. While kinases and phosphatases have been extensively studied, their organization and the mechanisms by which they balance each other are not well understood. To address these questions we performed quantitative analyses of large-scale 'omics' datasets from yeast, fly, plant, mouse and human. We uncovered an asymmetric balance of a previously-hidden scale: Each organism contained many different kinase genes, and these were balanced by a small set of highly abundant phosphatase proteins. Kinases were much more responsive to perturbations at the gene and protein levels. In addition, kinases had diverse scales of phenotypic impact when manipulated. Phosphatases, in contrast, were stable, highly robust and flatly organized, with rather uniform impact downstream. We validated aspects of this organization experimentally in nematode, and supported additional aspects by theoretic analysis of the dynamics of protein phosphorylation. Our analyses explain the empirical bias in the protein phosphorylation field toward characterization and therapeutic targeting of kinases at the expense of phosphatases. We show quantitatively and broadly that this is not only a historical bias, but stems from wide-ranging differences in their organization and impact. The asymmetric balance between these opposing regulators of protein phosphorylation is also common to opposing regulators of two other post-translational modification systems, suggesting its fundamental value.
Indexed as
Identifiers
What OpenQuestion holds
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.