ArticlePloS one2014
Phosphorylation site dynamics of early T-cell receptor signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 66 citations in OpenAlex.
- Multi-organ proteomic atlas of obesity regression in male mice.Nature metabolism · 2026Article
- The Y105 phosphosite between the SH3.1 and SH3.2 domains of Nck1 regulates its binding to CD3ϵ.iScience · 2026Article
- CoDIAC: A comprehensive approach for interaction analysis provides insights into SH2 domain function and regulation.Science signaling · 2025Article
- CoDIAC: A comprehensive approach for interaction analysis reveals novel insights into SH2 domain function and regulation.bioRxiv : the preprint server for biology · 2025Article
- Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.Cellular & molecular immunology · 2025Review
- Comprehensive evaluation of phosphoproteomic-based kinase activity inference.Nature communications · 2025Article
- From TCR fundamental research to innovative chimeric antigen receptor design.Nature reviews. Immunology · 2025Review
- The Constrained Disorder Principle Overcomes the Challenges of Methods for Assessing Uncertainty in Biological Systems.Journal of personalized medicine · 2024Review
- Targeted Quantification of Protein Phosphorylation and Its Contributions towards Mathematical Modeling of Signaling Pathways.Molecules (Basel, Switzerland) · 2023Review
- KSTAR: An algorithm to predict patient-specific kinase activities from phosphoproteomic data.Nature communications · 2022Article
- Article
- Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases.International journal of molecular sciences · 2020Article
- Modeling immune cell behavior across scales in cancer.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Computational Verification of Large Logical Models-Application to the Prediction of T Cell Response to Checkpoint Inhibitors.Frontiers in physiology · 2020Article
- Parameter Estimation and Uncertainty Quantification for Systems Biology Models.Current opinion in systems biology · 2019Article
- Article
- Generalizing Gillespie's Direct Method to Enable Network-Free Simulations.Bulletin of mathematical biology · 2019Article
- Scaling methods for accelerating kinetic Monte Carlo simulations of chemical reaction networks.The Journal of chemical physics · 2019Article
- An immunoproteomic approach to characterize the CAR interactome and signalosome.Science signaling · 2019Article
- Understanding the Dynamics of T-Cell Activation in Health and Disease Through the Lens of Computational Modeling.JCO clinical cancer informatics · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
In adaptive immune responses, T-cell receptor (TCR) signaling impacts multiple cellular processes and results in T-cell differentiation, proliferation, and cytokine production. Although individual protein-protein interactions and phosphorylation events have been studied extensively, we lack a systems-level understanding of how these components cooperate to control signaling dynamics, especially during the crucial first seconds of stimulation. Here, we used quantitative proteomics to characterize reshaping of the T-cell phosphoproteome in response to TCR/CD28 co-stimulation, and found that diverse dynamic patterns emerge within seconds. We detected phosphorylation dynamics as early as 5 s and observed widespread regulation of key TCR signaling proteins by 30 s. Development of a computational model pointed to the presence of novel regulatory mechanisms controlling phosphorylation of sites with central roles in TCR signaling. The model was used to generate predictions suggesting unexpected roles for the phosphatase PTPN6 (SHP-1) and shortcut recruitment of the actin regulator WAS. Predictions were validated experimentally. This integration of proteomics and modeling illustrates a novel, generalizable framework for solidifying quantitative understanding of a signaling network and for elucidating missing links.
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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.