ArticleMolecular and cellular biology1996
Distinct tyrosine phosphorylation sites in ZAP-70 mediate activation and negative regulation of antigen receptor function.
Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 141 citations in OpenAlex.
- Structural Identification of Major Molecular Determinants for Phosphotyrosine Recognition in Tyrosine Kinases Reveals Tumour Promoting and Suppressive Functions.bioRxiv : the preprint server for biology · 2025Article
- HIV Nef disrupts Lck signaling by inducing aberrant phosphorylation of its substrates.ImmunoHorizons · 2025Article
- MMFuncPhos: A Multi-Modal Learning Framework for Identifying Functional Phosphorylation Sites and Their Regulatory Types.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cyclophilin A associates with and regulates the activity of ZAP70 in TCR/CD3-stimulated T cells.Cellular and molecular life sciences : CMLS · 2022Article
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- SILAC Phosphoproteomics Reveals Unique Signaling Circuits in CAR-T Cells and the Inhibition of B Cell-Activating Phosphorylation in Target Cells.Journal of proteome research · 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
- Encoding optical control in LCK kinase to quantitatively investigate its activity in live cells.Nature structural & molecular biology · 2017Article
- A PLC-γ1 Feedback Pathway Regulates Lck Substrate Phosphorylation at the T-Cell Receptor and SLP-76 Complex.Journal of proteome research · 2017Article
- SRC homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) N-terminal tyrosine residues regulate a dynamic signaling equilibrium involving feedback of proximal T-cell receptor (TCR) signaling.Molecular & cellular proteomics : MCP · 2015Article
- Monitoring the immune response to vaccination with an inactivated vaccine associated to bovine neonatal pancytopenia by deep sequencing transcriptome analysis in cattle.Veterinary research · 2013Article
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- Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells.PloS one · 2012Article
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- A discrete affinity-driven elevation of ZAP-70 kinase activity initiates negative selection.Journal of receptor and signal transduction research · 2010Article
- Tyrosines in the carboxyl terminus regulate Syk kinase activity and function.The Journal of biological chemistry · 2010Article
- ZAP-70: an essential kinase in T-cell signaling.Cold Spring Harbor perspectives in biology · 2010Review
- Organization of proximal signal initiation at the TCR:CD3 complex.Immunological reviews · 2009Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Biochemical and genetic evidence has implicated two families of protein tyrosine kinases (PTKs), the Src- and Syk-PTKs, in T- and B-cell antigen receptor signaling. ZAP-70 is a member of the Syk-PTKs that associates with the T-cell antigen receptor and undergoes tyrosine phosphorylation following receptor activation. Three tyrosine residues, Tyr-292, -492, and -493, have been identified as sites of phosphorylation following T-cell antigen receptor engagement. Utilizing ZAP-70- and Syk-deficient lymphocytes (Syk-DT40 cells), we provide biochemical and functional evidence that heterologous trans-phosphorylation of Tyr-493 by a Src-PTK is required for antigen receptor-mediated activation of both the calcium and ras pathways. In contrast, cells expressing mutations at Tyr-292 or -492 demonstrate hyperactive T- and B-cell antigen receptor phenotypes. Thus, phosphorylation of ZAP-70 mediates both activation and inactivation of antigen receptor signaling.
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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.