ArticleThe Journal of biological chemistry2008
Inhibition of ZAP-70 kinase activity via an analog-sensitive allele blocks T cell receptor and CD28 superagonist signaling.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Construction of anti-tumor immune gene signature for HNSCC and identification of 4'-Hydroxywogonin as a potential immunotherapy combination drug.Cancer cell international · 2025Article
- PTPN22-CD45 dual phosphatase retrograde feedback enhances TCR signaling and autoimmunity.Science advances · 2025Article
- Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases.Immunity · 2024Article
- 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
- Naturally Occurring Genetic Alterations in Proximal TCR Signaling and Implications for Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Immunopharmacology and Quantitative Analysis of Tyrosine Kinase Signaling.Current protocols in immunology · 2020Article
- ZAP-70 Shapes the Immune Microenvironment in B Cell Malignancies.Frontiers in oncology · 2020Review
- Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70.Nature communications · 2018Article
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
- Engineering a Dual Small Molecule Gated ZAP70 Switch in T Cells.ACS synthetic biology · 2018Article
- Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions.Cell reports · 2018Article
- A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45.Molecular cell · 2017Article
- Self-Recognition Sensitizes Mouse and Human Regulatory T Cells to Low-Dose CD28 Superagonist Stimulation.Frontiers in immunology · 2017Article
- CD28 Costimulation: From Mechanism to Therapy.Immunity · 2016Review
- Syk Is Recruited to Stress Granules and Promotes Their Clearance through Autophagy.The Journal of biological chemistry · 2015Article
- Allele-sensitive mutant, Itkas, reveals that Itk kinase activity is required for Th1, Th2, Th17, and iNKT-cell cytokine production.European journal of immunology · 2015Article
- The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway.Science signaling · 2015Article
- The Timing of T Cell Priming and Cycling.Frontiers in immunology · 2015Review
- CD28 co-stimulation in T-cell homeostasis: a recent perspective.ImmunoTargets and therapy · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
ZAP-70 is a cytoplasmic protein tyrosine kinase that is required for T cell antigen receptor (TCR) signaling. Both mice and humans deficient in ZAP-70 fail to develop functional T cells, thus demonstrating its necessity for T cell development and function. There is currently no highly specific, cell-permeable, small molecule inhibitor for ZAP-70; therefore, we generated a mutant ZAP-70 allele that retains kinase activity but is sensitive to inhibition by a mutant-specific inhibitor. We validated the chemical genetic inhibitor system in Jurkat T cell lines, where the inhibitor blocked ZAP-70-dependent TCR signaling in cells expressing the analog-sensitive allele. Interestingly, the inhibitor also ablated CD28 superagonist signaling, thereby demonstrating the utility of this system in dissecting the requirement for ZAP-70 in alternative mechanisms of T cell activation. Thus, we have developed the first specific chemical means of inhibiting ZAP-70 in cells, which serves as a valuable tool for studying the function of ZAP-70 in T cells.
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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.