ArticleMolecular and cellular biology2005
Intramolecular regulatory switch in ZAP-70: analogy with receptor tyrosine kinases.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
77 citing papers in PubMed, 127 citations in OpenAlex.
- Repurposing Tyrosine Kinase Inhibitors for Sickle Cell Disease: Focus on Band 3 Phosphorylation.Biomedicines · 2026Review
- AFrontiers in immunology · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Efficient Isolation and Enrichment of SH2 Domain Protein Species from Plasma Exploiting Specific Peptide-Protein Interactions.ACS omega · 2025Article
- HIV Nef disrupts Lck signaling by inducing aberrant phosphorylation of its substrates.ImmunoHorizons · 2025Article
- Article
- THEMIS is a substrate and allosteric activator of SHP1, playing dual roles during T cell development.Nature structural & molecular biology · 2024Article
- 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
- Kinetic proofreading through the multi-step activation of the ZAP70 kinase underlies early T cell ligand discrimination.Nature immunology · 2022Article
- ZAP70, too little, too much can lead to autoimmunity.Immunological reviews · 2022Review
- Regulating the discriminatory response to antigen by T-cell receptor.Bioscience reports · 2022Review
- Negative Regulation of Zap70 by Lck Forms the Mechanistic Basis of Differential Expression in CD4 and CD8 T Cells.Frontiers in immunology · 2022Article
- Acute Csk inhibition hinders B cell activation by constraining the PI3 kinase pathway.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Positive feedback between the T cell kinase Zap70 and its substrate LAT acts as a clustering-dependent signaling switch.Cell reports · 2021Article
- Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer.Molecular cell · 2021Article
- A disease-associated mutation that weakens ZAP70 autoinhibition enhances responses to weak and self-ligands.Science signaling · 2021Article
- Mechanisms determining a differential threshold for sensing Src family kinase activity by B and T cell antigen receptors.The Journal of biological chemistry · 2020Article
- Targeting Cancer Stem Cells by Genetically Engineered Chimeric Antigen Receptor T Cells.Frontiers in genetics · 2020Review
- Tuning ITAM multiplicity on T cell receptors can control potency and selectivity to ligand density.Science signaling · 2018Article
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
17 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
5 authors at 2 institutions in 2 countries.
Funding
Abstract
ZAP-70, a Syk family cytoplasmic protein tyrosine kinase (PTK), is required to couple the activated T-cell antigen receptor (TCR) to downstream signaling pathways. It contains two tandem SH2 domains that bind to phosphorylated TCR subunits and a C-terminal catalytic domain. The region connecting the SH2 domains with the kinase domain, termed interdomain B, has previously been shown to have striking regulatory effects on ZAP-70 function, presumed to be due to the recruitment of key substrates. Paradoxically, deletion of interdomain B preserves ZAP-70 function. Recent structural studies of several receptor tyrosine kinases (RTKs) revealed that their juxtamembrane regions negatively regulate their catalytic activities. In EphB2 and several other RTKs, this autoinhibition depends upon interaction between the kinase domain and tyrosine residues within the juxtamembrane region. Autoinhibition is released when these tyrosines become phosphorylated following receptor stimulation. Sequence homology suggested analogous regulation for ZAP-70. Based on mutagenesis analysis of ZAP-70 interdomain B, we find that this region downregulates ZAP-70 catalytic activity in a similar manner as the juxtamembrane region of EphB2. Similar regulation was also noted for the related Syk kinase. These findings suggest that a general autoinhibitory mechanism employed by RTKs is also used by some cytoplasmic tyrosine kinases.
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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.