ArticleProceedings of the National Academy of Sciences of the United States of America2022
Dephosphorylation accelerates the dissociation of ZAP70 from the T cell receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- Stiff matrix impairs cytotoxic T lymphocyte function at multiple levels.Science advances · 2026Article
- Improvement in model flexibility reveals signaling pathway in T cell responses to pulsatile stimuli.NPJ systems biology and applications · 2026Article
- Multivalent adaptor networks generate nanoscale organisation within T cell signalling condensates.bioRxiv : the preprint server for biology · 2026Article
- Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors.Nature biomedical engineering · 2026Article
- Murine T-cell receptor OT-I exhibits imperfect discrimination between foreign and self-antigens.The EMBO journal · 2026Article
- Parallel reactions on a single T cell receptor offer a robust kinetic proofreading mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- Quantitative Analysis of Protein-Protein Equilibrium Constants in Cellular Environments Using Single-Molecule Localization Microscopy.Nano letters · 2024Article
- Differential roles of kinetic on- and off-rates in T-cell receptor signal integration revealed with a modified Fab'-DNA ligand.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mechanical force matters in early T cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation.Science advances · 2024Article
- Mechanical control of antigen detection and discrimination by T and B cell receptors.Biophysical journal · 2024Review
- The quantum model of T-cell activation: Revisiting immune response theories.Scandinavian journal of immunology · 2024Article
- Differential Roles of Kinetic On- and Off-Rates in T-Cell Receptor Signal Integration Revealed with a Modified Fab'-DNA Ligand.bioRxiv : the preprint server for biology · 2024Article
- Mechanical forces amplify TCR mechanotransduction in T cell activation and function.Applied physics reviews · 2024Review
- Modulation of antigen discrimination by duration of immune contacts in a kinetic proofreading model of T cell activation with extreme statistics.PLoS computational biology · 2023Article
- Physical-Chemical Regulation of Membrane Receptors Dynamics in Viral Invasion and Immune Defense.Journal of molecular biology · 2023Review
- Article
- The discriminatory power of the T cell receptor.eLife · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Protein-protein binding domains are critical in signaling networks. Src homology 2 (SH2) domains are binding domains that interact with sequences containing phosphorylated tyrosines. A subset of SH2 domain-containing proteins has tandem domains, which are thought to enhance binding affinity and specificity. However, a trade-off exists between long-lived binding and the ability to rapidly reverse signaling, which is a critical requirement of noise-filtering mechanisms such as kinetic proofreading. Here, we use modeling to show that the unbinding rate of tandem, but not single, SH2 domains can be accelerated by phosphatases. Using surface plasmon resonance, we show that the phosphatase CD45 can accelerate the unbinding rate of zeta chain-associated protein kinase 70 (ZAP70), a tandem SH2 domain-containing kinase, from biphosphorylated peptides from the T cell receptor (TCR). An important functional prediction of accelerated unbinding is that the intracellular ZAP70-TCR half-life in T cells will not be fixed but rather, dependent on the extracellular TCR-antigen half-life, and we show that this is the case in both cell lines and primary T cells. The work highlights that tandem SH2 domains can break the trade-off between signal fidelity (requiring long half-life) and signal reversibility (requiring short half-life), which is a key requirement for T cell antigen discrimination mediated by kinetic proofreading.
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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.