ArticleeLife2016
An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 101 citations in OpenAlex.
- LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synthetic Substrate Discovery for Hck Kinase via Phage Display.Biochemistry · 2026Article
- Context-dependent peptide recognition shapes tyrosine kinase substrate specificity beyond consensus motifs.bioRxiv : the preprint server for biology · 2026Article
- Profiling tyrosine kinase substrate recognition using bacterial peptide display and deep sequencing.bioRxiv : the preprint server for biology · 2025Article
- 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
- Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire.Nature immunology · 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
- Proofreading and single-molecule sensitivity in T cell receptor signaling by condensate nucleation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- An engineered viral protein activates STAT5 to prevent T cell suppression.Science immunology · 2025Article
- SYK negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- SCREEN: A Graph-based Contrastive Learning Tool to Infer Catalytic Residues and Assess Enzyme Mutations.Genomics, proteomics & bioinformatics · 2025Article
- The LAT Rheostat as a Regulator of Megakaryocyte Activation.Thrombosis and haemostasis · 2024Article
- Spleen Tyrosine Kinase (SYK) negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.bioRxiv : the preprint server for biology · 2024Article
- Article
- Article
- A Story of Kinases and Adaptors: The Role of Lck, ZAP-70 and LAT in Switch Panel Governing T-Cell Development and Activation.Biology · 2023Review
- A single-amino acid substitution in the adaptor LAT accelerates TCR proofreading kinetics and alters T-cell selection, maintenance and function.Nature immunology · 2023Article
- Article
- Crystal structure of the kinase domain of a receptor tyrosine kinase from a choanoflagellate, Monosiga brevicollis.PloS one · 2023Article
- Identification of GC-rich LAT genes in birds.PloS one · 2023Article
5 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 3 institutions in 1 country.
Funding
Abstract
The sequence of events that initiates T cell signaling is dictated by the specificities and order of activation of the tyrosine kinases that signal downstream of the T cell receptor. Using a platform that combines exhaustive point-mutagenesis of peptide substrates, bacterial surface-display, cell sorting, and deep sequencing, we have defined the specificities of the first two kinases in this pathway, Lck and ZAP-70, for the T cell receptor ζ chain and the scaffold proteins LAT and SLP-76. We find that ZAP-70 selects its substrates by utilizing an electrostatic mechanism that excludes substrates with positively-charged residues and favors LAT and SLP-76 phosphosites that are surrounded by negatively-charged residues. This mechanism prevents ZAP-70 from phosphorylating its own activation loop, thereby enforcing its strict dependence on Lck for activation. The sequence features in ZAP-70, LAT, and SLP-76 that underlie electrostatic selectivity likely contribute to the specific response of T cells to foreign antigens.
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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.