ArticleProceedings of the National Academy of Sciences of the United States of America2009
Stability of an autoinhibitory interface in the structure of the tyrosine kinase ZAP-70 impacts T cell receptor response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- HIV Nef disrupts Lck signaling by inducing aberrant phosphorylation of its substrates.ImmunoHorizons · 2025Article
- Generation of antitumor chimeric antigen receptors incorporating T cell signaling motifs.Science signaling · 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
- Article
- ZAP70, too little, too much can lead to autoimmunity.Immunological reviews · 2022Review
- Dephosphorylation accelerates the dissociation of ZAP70 from the T cell receptor.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A disease-associated mutation that weakens ZAP70 autoinhibition enhances responses to weak and self-ligands.Science signaling · 2021Article
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
- Src homology 2 domains enhance tyrosine phosphorylationThe Journal of biological chemistry · 2018Article
- Review
- Destabilizing the autoinhibitory conformation of Zap70 induces up-regulation of inhibitory receptors and T cell unresponsiveness.The Journal of experimental medicine · 2017Article
- 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
- Non-degradative Ubiquitination of Protein Kinases.PLoS computational biology · 2016Article
- T cell receptor dwell times control the kinase activity of Zap70.Nature 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
- Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding.The Biochemical journal · 2015Article
- CD25 and CD69 induction by α4β1 outside-in signalling requires TCR early signalling complex proteins.The Biochemical journal · 2013Article
- Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker.Molecular and cellular biology · 2013Article
- Monovalent and multivalent ligation of the B cell receptor exhibit differential dependence upon Syk and Src family kinases.Science signaling · 2013Article
- Article
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 4 institutions in 1 country.
Funding
Abstract
The delivery of signals from the activated T cell antigen receptor (TCR) inside the cell relies on the protein tyrosine kinase ZAP-70 (zeta-associated protein of 70 kDa). A recent crystal structure of inactive full-length ZAP-70 suggests that a central interface formed by the docking of the two SH2 domains of ZAP-70 onto the kinase domain is crucial for suppressing catalytic activity. Here we validate the significance of this autoinhibitory interface for the regulation of ZAP-70 catalytic activity and the T cell response. For this purpose, we perform in vitro catalytic activity assays and binding experiments using ZAP-70 proteins purified from insect cells to examine activation of ZAP-70. Furthermore, we use cell lines stably expressing wild-type or mutant ZAP-70 to monitor proximal events in T cell signaling, including TCR-induced phosphorylation of ZAP-70 substrates, activation of the MAP kinase pathway, and intracellular Ca(2+) levels. Taken together, our results directly correlate the stability of the autoinhibitory interface with the activation of these key events in the T cell response.
Indexed as
Identifiers
What OpenQuestion holds
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.