ArticleMolecular and cellular biology1996
Enhancement of lymphocyte responsiveness by a gain-of-function mutation of ZAP-70.
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 32 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
32 citing papers in PubMed, 89 citations in OpenAlex.
- Phosphorylation at Y317 on Syk negatively regulates both ITAM- and hemITAM-mediated signaling and function in platelets.Blood advances · 2025Article
- SYK negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Spleen Tyrosine Kinase (SYK) negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.bioRxiv : the preprint server for biology · 2024Article
- [A highly sensitive approach for the analysis of tyrosine phosphoproteome in primary T cells].Se pu = Chinese journal of chromatography · 2024Article
- Cyclophilin A associates with and regulates the activity of ZAP70 in TCR/CD3-stimulated T cells.Cellular and molecular life sciences : CMLS · 2022Article
- Beyond the Cell Surface: Targeting Intracellular Negative Regulators to Enhance T cell Anti-Tumor Activity.International journal of molecular sciences · 2019Review
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
- The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway.Science signaling · 2015Article
- Signaling of the ITK (interleukin 2-inducible T cell kinase)-SYK (spleen tyrosine kinase) fusion kinase is dependent on adapter SLP-76 and on the adapter function of the kinases SYK and ZAP70.The Journal of biological chemistry · 2013Article
- Tyrosines in the carboxyl terminus regulate Syk kinase activity and function.The Journal of biological chemistry · 2010Article
- ZAP70: a master regulator of adaptive immunity.Seminars in immunopathology · 2010Review
- ZAP-70: an essential kinase in T-cell signaling.Cold Spring Harbor perspectives in biology · 2010Review
- Syk and pTyr'd: Signaling through the B cell antigen receptor.Biochimica et biophysica acta · 2009Review
- SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels.Immunological reviews · 2009Review
- ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia.Blood · 2008Article
- Allelic variant in CTLA4 alters T cell phosphorylation patterns.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Coupling Ca2+ store release to Icrac channel activation in B lymphocytes requires the activity of Lyn and Syk kinases.The Journal of cell biology · 2007Article
- c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses.The Biochemical journal · 2005Review
- A mouse with a loss-of-function mutation in the c-Cbl TKB domain shows perturbed thymocyte signaling without enhancing the activity of the ZAP-70 tyrosine kinase.The Journal of experimental medicine · 2003Article
- The non-receptor tyrosine kinase Syk is a target of Cbl-mediated ubiquitylation upon B-cell receptor stimulation.The EMBO journal · 2001Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protein tyrosine kinase ZAP-70 plays an essential role in T-cell activation and development. After T-cell receptor stimulation, ZAP-70 is associated with the receptor and is phosphorylated on many tyrosine residues, including tyrosine 292 (Y-292), in the region between the C-terminal SH2 domain and the kinase domain (interdomain B). Here we show that a mutation of Y-292 (292F) or deletion of interdomain B enhanced the ability of ZAP-70 to reconstitute B-cell receptor stimulation-dependent NF-AT induction in a B-cell line deficient in Syk. In contrast, in a T-cell line, expression of 292F led to basal NF-AT induction independent of T-cell receptor stimulation. These results demonstrate that the role of Y-292 is to negatively regulate the function of ZAP-70 in lymphocytes. This appears to be a dominant function of interdomain B because deletion of most of interdomain B also resulted in a mutant of ZAP-70 with enhanced ability to reconstitute Syk-deficient DT-40 B cells. Since our biochemical studies did not reveal an effect of the 292F mutation on either the kinase activity of ZAP-70 or on the ability of ZAP-70 to bind to the receptor, we propose a model in which Y-292 interacts with an inhibitory protein to negatively regulate ZAP-70 function.
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.