ArticleThe Journal of experimental medicine2007
Distinct roles for Syk and ZAP-70 during early thymocyte development.
Article in The Journal of experimental medicine, 2007. 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, 84 citations in OpenAlex.
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Conservation of NLRP3 Inflammasome Pathway in Monotremes and Large-Scale Restructuring of the Caspase-1 Gene Cluster Region in Mammals.Journal of molecular evolution · 2026Article
- Development of αβ and γδ T Cells in the Thymus and Methods of Analysis.International journal of molecular sciences · 2025Review
- Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire.Nature immunology · 2025Article
- Benchmarking spleen tyrosine kinase (Syk) expression in T- and NK-cell neoplasms: Implications for therapeutic targeting.British journal of haematology · 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
- SOX9 drives KRAS-induced lung adenocarcinoma progression and suppresses anti-tumor immunity.Oncogene · 2023Article
- Combined immunodeficiency caused by pathogenic variants in theFrontiers in immunology · 2023Article
- ZAP70, too little, too much can lead to autoimmunity.Immunological reviews · 2022Review
- Single-cell transcriptomics uncovers an instructive T-cell receptor role in adult γδ T-cell lineage commitment.The EMBO journal · 2022Article
- Lipid metabolism in autoimmune rheumatic disease: implications for modern and conventional therapies.The Journal of clinical investigation · 2022Review
- Spleen tyrosine kinase mediates the γδTCR signaling required for γδT cell commitment and γδT17 differentiation.Frontiers in immunology · 2022Article
- Negative Regulation of Zap70 by Lck Forms the Mechanistic Basis of Differential Expression in CD4 and CD8 T Cells.Frontiers in immunology · 2022Article
- NR4A family members regulate T cell tolerance to preserve immune homeostasis and suppress autoimmunity.JCI insight · 2021Article
- A divergent transcriptional landscape underpins the development and functional branching of MAIT cells.Science immunology · 2019Article
- ZAP-70 Regulates Autoimmune Arthritis via Alterations in T Cell Activation and Apoptosis.Cells · 2019Article
- Cutting Edge: HDAC3 Protects Double-Positive Thymocytes from P2X7 Receptor-Induced Cell Death.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- T cell receptor signaling for γδT cell development.Inflammation and regeneration · 2019Review
- Correction of T cell deficiency in ZAP-70 knock-out mice by simple intraperitoneal adoptive transfer of thymocytes.Clinical and experimental immunology · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The spleen tyrosine kinase (Syk) and zeta-associated protein of 70 kD (ZAP-70) tyrosine kinases are both expressed during early thymocyte development, but their unique thymic functions have remained obscure. No specific role for Syk during beta-selection has been established, and no role has been described for ZAP-70 before positive selection. We show that Syk and ZAP-70 provide thymocytes with unique and separable fitness advantages during early development. Syk-deficient, but not ZAP-70-deficient, thymocytes are specifically impaired in initial pre-TCR signaling at the double-negative (DN) 3 beta selection stage and show reduced cell-cycle entry. Surprisingly, and despite overlapping expression of both kinases, only ZAP-70 appears to promote sustained pre-TCR/TCR signaling during the DN4, immature single-positive, and double-positive stages of development before thymic selection occurs. ZAP-70 promotes survival and cell-cycle progression of developing thymocytes before positive selection, as also shown by in vivo anti-CD3 treatment of recombinase-activating gene 1-deficient mice. Our results establish a temporal separation of Syk family kinase function during early thymocyte development and a novel role for ZAP-70. We propose that pre-TCR signaling continues during DN4 and later stages, with ZAP-70 dynamically replacing Syk for continued pre-TCR 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.