ArticleNature immunology2019
Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.
Article in Nature immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Pooled it
- LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Weak SLP-76/PLC-γ1 interaction fine-tunes T cell receptor signal strength to optimize T cell responsiveness.Nature communications · 2026Article
- Article
- Chimeric switch scaffold protein augments CAR synapse formation and signaling networks.Journal for immunotherapy of cancer · 2026Article
- Potassium suppresses allosteric activation of ZAP-70-dependent T cell receptor signaling.The Journal of biological chemistry · 2026Article
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- Phosphoproteomic analysis of successive Jurkat CD19-CAR generations reveals TCRζ-driven signalling.Cellular signalling · 2026Article
- Murine T-cell receptor OT-I exhibits imperfect discrimination between foreign and self-antigens.The EMBO journal · 2026Article
- Low Levels of Mouse γδ T Cell Development Persist in the Presence of Null Mutants of the LAT Adaptor.International journal of molecular sciences · 2025Article
- Engineering T cells with a membrane-tethered version of SLP-76 overcomes antigen-low resistance to CAR T cell therapy.Nature cancer · 2025Article
- Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire.Nature immunology · 2025Article
- T cell costimulatory and inhibitory signals differentially modulate LAT condensate nucleation propensity after TCR ligation.bioRxiv : the preprint server for biology · 2025Article
- BTK autoinhibition analyzed by high-throughput swaps of SH2 domains.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- 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
- Synthetic signaling platform uncovers and rewires cellular responses to PD-1 perturbation.bioRxiv : the preprint server for biology · 2025Article
- Regulation of TCR-induced Transcriptional Kinetics by Interleukin 2-inducible T Cell Kinase (ITK) in CD8bioRxiv : the preprint server for biology · 2025Article
- Weak SLP-76-PLC-γ1 interaction in the LAT-nucleated multi-protein complex fine-tunes TCR signal strength to optimize T cell responsiveness.bioRxiv : the preprint server for biology · 2025Article
- PTPN22-CD45 dual phosphatase retrograde feedback enhances TCR signaling and autoimmunity.Science advances · 2025Article
- G-Protein-Coupled Receptor Kinase 2 Limits CCL21-Induced T Cell Migration via Phospholipase Cγ1.Receptors (Basel, Switzerland) · 2025Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 8 institutions in 2 countries.
Funding
Abstract
Self-non-self discrimination is central to T cell-mediated immunity. The kinetic proofreading model can explain T cell antigen receptor (TCR) ligand discrimination; however, the rate-limiting steps have not been identified. Here, we show that tyrosine phosphorylation of the T cell adapter protein LAT at position Y132 is a critical kinetic bottleneck for ligand discrimination. LAT phosphorylation at Y132, mediated by the kinase ZAP-70, leads to the recruitment and activation of phospholipase C-γ1 (PLC-γ1), an important effector molecule for T cell activation. The slow phosphorylation of Y132, relative to other phosphosites on LAT, is governed by a preceding glycine residue (G131) but can be accelerated by substituting this glycine with aspartate or glutamate. Acceleration of Y132 phosphorylation increases the speed and magnitude of PLC-γ1 activation and enhances T cell sensitivity to weaker stimuli, including weak agonists and self-peptides. These observations suggest that the slow phosphorylation of Y132 acts as a proofreading step to facilitate T cell ligand discrimination.
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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.