ArticleThe Journal of experimental medicine2001
T cell development and T cell responses in mice with mutations affecting tyrosines 292 or 315 of the ZAP-70 protein tyrosine kinase.
Article in The Journal of experimental medicine, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 56 citations in OpenAlex.
- AFrontiers in immunology · 2026Article
- HIV Nef disrupts Lck signaling by inducing aberrant phosphorylation of its substrates.ImmunoHorizons · 2025Article
- Nck1 regulates the in vitro development of human regulatory T cells through AKT pathway.Clinical and experimental immunology · 2025Article
- 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
- Negative Regulation of Zap70 by Lck Forms the Mechanistic Basis of Differential Expression in CD4 and CD8 T Cells.Frontiers in immunology · 2022Article
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
- Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- T cell receptor dwell times control the kinase activity of Zap70.Nature immunology · 2015Article
- Vav1 Regulates T-Cell Activation through a Feedback Mechanism and Crosstalk between the T-Cell Receptor and CD28.Journal of proteome research · 2015Article
- The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway.Science signaling · 2015Article
- Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications.American journal of clinical and experimental immunology · 2014Review
- Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker.Molecular and cellular biology · 2013Article
- Quantitative phosphoproteomic analysis of T cell receptor signaling in diabetes prone and resistant mice.Journal of proteome research · 2010Article
- ZAP70: a master regulator of adaptive immunity.Seminars in immunopathology · 2010Review
- ZAP-70: an essential kinase in T-cell signaling.Cold Spring Harbor perspectives in biology · 2010Review
- Stability of an autoinhibitory interface in the structure of the tyrosine kinase ZAP-70 impacts T cell receptor response.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Organization of proximal signal initiation at the TCR:CD3 complex.Immunological reviews · 2009Review
- A hypomorphic allele of ZAP-70 reveals a distinct thymic threshold for autoimmune disease versus autoimmune reactivity.The Journal of experimental medicine · 2009Article
- Syk and pTyr'd: Signaling through the B cell antigen receptor.Biochimica et biophysica acta · 2009Review
- Allelic variant in CTLA4 alters T cell phosphorylation patterns.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
After stimulation of the T cell receptor (TCR), the tyrosine residues 292 and 315 in interdomain B of the protein tyrosine kinase ZAP-70 become phosphorylated and plausibly function as docking sites for Cbl and Vav1, respectively. The two latter proteins have been suggested to serve as substrates for ZAP-70 and to fine-tune its function. To address the role of these residues in T cell development and in the function of primary T cells, we have generated mice that express ZAP-70 molecules with Tyr to Phe substitution at position 292 (Y292F) or 315 (Y315F). When analyzed in a sensitized TCR transgenic background, the ZAP-70 Y315F mutation reduced the rate of positive selection and delayed the occurrence of negative selection. Furthermore, this mutation unexpectedly affected the constitutive levels of the CD3-zeta p21 phosphoisoform. Conversely, the ZAP-70 Y292F mutation upregulated proximal events in TCR signaling and allowed more T cells to produce interleukin 2 and interferon gamma in response to a given dose of antigen. The observation that ZAP-70 Y292F T cells have a slower rate of ligand-induced TCR downmodulation suggests that Y292 is likely involved in regulating the duration activated TCR reside at the cell surface. Furthermore, we showed that Y292 and Y315 are dispensable for the TCR-induced tyrosine phosphorylation of Cbl and Vav1, respectively. Therefore, other molecules present in the TCR signaling cassette act as additional adaptors for Cbl and Vav1. The present in vivo analyses extend previous data based on transformed T cell lines and suggest that residue Y292 plays a role in attenuation of TCR signaling, whereas residue Y315 enhances ZAP-70 function.
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