ArticleThe Journal of experimental medicine1996
Dominant-negative zeta-associated protein 70 inhibits T cell antigen receptor signaling.
Article in The Journal of experimental medicine, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 99 citations in OpenAlex.
- Avoidance of related donors in CAEBV with germline immune variants: long-termoutcome of matched unrelated donor HSCT - a case report.Annals of hematology · 2026Article
- Negative Regulation of Zap70 by Lck Forms the Mechanistic Basis of Differential Expression in CD4 and CD8 T Cells.Frontiers in immunology · 2022Article
- CRASH-IT Switch Enables Reversible and Dose-Dependent Control of TCR and CAR T-cell Function.Cancer immunology research · 2021Article
- Light-Controlled Affinity Purification of Protein Complexes Exemplified by the Resting ZAP70 Interactome.Frontiers in immunology · 2019Article
- Downregulation of CD3ζ in NK Cells from Systemic Lupus Erythematosus Patients Confers a Proinflammatory Phenotype.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
- Article
- Src homology 2 domains enhance tyrosine phosphorylationThe Journal of biological chemistry · 2018Article
- Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen.SLAS discovery : advancing life sciences R & D · 2017Article
- Zap70 inhibits Syk-mediated osteoclast function.Journal of cellular biochemistry · 2013Article
- Monovalent and multivalent ligation of the B cell receptor exhibit differential dependence upon Syk and Src family kinases.Science signaling · 2013Article
- Feedback circuits monitor and adjust basal Lck-dependent events in T cell receptor signaling.Science signaling · 2011Article
- Imaging T-cell receptor activation reveals accumulation of tyrosine-phosphorylated CD3ζ in the endosomal compartment.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia.Blood · 2008Article
- T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression.PLoS biology · 2003Article
- Systematic identification of regulatory proteins critical for T-cell activation.Journal of biology · 2003Article
- Zap-70-independent Ca(2+) mobilization and Erk activation in Jurkat T cells in response to T-cell antigen receptor ligation.Molecular and cellular biology · 2001Article
- Requirement for tyrosine residues 315 and 319 within zeta chain-associated protein 70 for T cell development.The Journal of experimental medicine · 2001Article
- Partially phosphorylated T cell receptor zeta molecules can inhibit T cell activation.The Journal of experimental medicine · 1999Article
- Adhesion to fibronectin promotes the activation of the p125(FAK)/Zap-70complex in human T cells.Immunology · 1999Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zeta-associated protein (ZAP)-70 is a cytoplasmic protein tyrosine required for T cell antigen receptor (TCR) signaling and development. Mutations in ZAP-70 result in severe combined immunodeficiency in humans. ZAP-70 interacts with the TCR by binding to tyrosine-phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) present in the invariant subunits of the TCR complex. Here we report that two ZAP-70 mutants devoid of kinase activity, generated either by a point mutation in the kinase domain to create an inactive kinase, or by truncation of the entire kinase domain (SH2[N+C]), functioned as dominant-negative mutants to specifically suppress TCR-mediated activation of NFAT, a nuclear factor essential for inducible interleukin 2 gene expression. Biochemical studies with the SH2(N+C) mutant showed that it also blocked early TCR signaling events, such as p95vav tyrosine phosphorylation, extracellular signal-regulated kinase 2 activation, and the association of a number of tyrosine-phosphorylated proteins with growth factor receptor-binding protein 2 (GRB2). The inhibitory effects of the SH2(N+C) mutant revealed that it requires an intact phosphotyrosine-binding site in its COOH-terminal SH2 domain. Using a CD8-zeta chimeric receptor to analyze the interaction of the SH2(N+C) mutant with ITAMs of TCR-zeta, we found that this mutant was constitutively bound to the hyperphosphorylated CD8-zeta chimera. These results indicate that tyrosine-phosphorylated ITAM is the target for the action of this dominant-negative mutant, suggesting that the assembly of a functional receptor signaling complex on ITAMs is a critical proximal TCR signaling event leading to downstream activation.
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