ArticleMolecular cell2021
Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- A prognostic model for head and neck squamous cell carcinoma based on eosinophil extracellular trap related genes.Translational cancer research · 2026Article
- Insights into PI3K/AKT signaling in B cell development and chronic lymphocytic leukemia.FEBS letters · 2025Review
- Common origins of autoimmune diseases and lymphoid malignancies.Trends in immunology · 2025Review
- SF3B1 mutation accelerates the development of CLL via activation of the mTOR pathway.JCI insight · 2025Article
- The Inositol-5-Phosphatase SHIP1: Expression, Regulation and Role in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- A hypoxia-derived gene signature to suggest cisplatin-based therapeutic responses in patients with cervical cancer.Computational and structural biotechnology journal · 2024Article
- Expression of variant isoforms of the tyrosine kinase SYK differentially regulates cervical cancer progression through PI3K/AKT pathway.Scientific reports · 2024Article
- Identification of shared gene signatures and biological mechanisms between preeclampsia and polycystic ovary syndrome.Heliyon · 2024Article
- ZAP-70 augments tonic B-cell receptor and CCR7 signaling in IGHV-unmutated chronic lymphocytic leukemia.Blood advances · 2024Article
- B cell receptor signaling and associated pathways in the pathogenesis of chronic lymphocytic leukemia.Frontiers in oncology · 2024Review
- AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived HJournal of Cancer · 2024Article
- Identification of bladder cancer subtypes and predictive model for prognosis, immune features, and immunotherapy based on neutrophil extracellular trap-related genes.Scientific reports · 2023Article
- [Transcriptome sequencing for identification of the genes associated with restenosis of venous grafts in rabbits].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Immunomodulatory role of spleen tyrosine kinase in chronic inflammatory and autoimmune diseases.Immunity, inflammation and disease · 2023Review
- Spleen tyrosine kinase (SYK) signals are implicated in cardio-cerebrovascular diseases.Heliyon · 2023Review
- Identification of a Prognostic Model Based on Fatty Acid Metabolism-Related Genes of Head and Neck Squamous Cell Carcinoma.Frontiers in genetics · 2022Article
- B Lineage Cells in ANCA-Associated Vasculitis.International journal of molecular sciences · 2021Review
- Resistance Mutations to BTK Inhibitors Originate From the NF-κB but Not From the PI3K-RAS-MAPK Arm of the B Cell Receptor Signaling Pathway.Frontiers in immunology · 2021Review
- ZAP70 Activation Compensates for Loss of Class IA PI3K Isoforms Through Activation of the JAK-STAT3 Pathway.Cancer diagnosis & prognosisArticle
Corrections and comments
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Authors and funding
30 authors at 11 institutions in 5 countries.
Funding
Abstract
Even though SYK and ZAP70 kinases share high sequence homology and serve analogous functions, their expression in B and T cells is strictly segregated throughout evolution. Here, we identified aberrant ZAP70 expression as a common feature in a broad range of B cell malignancies. We validated SYK as the kinase that sets the thresholds for negative selection of autoreactive and premalignant clones. When aberrantly expressed in B cells, ZAP70 competes with SYK at the BCR signalosome and redirects SYK from negative selection to tonic PI3K signaling, thereby promoting B cell survival. In genetic mouse models for B-ALL and B-CLL, conditional expression of Zap70 accelerated disease onset, while genetic deletion impaired malignant transformation. Inducible activation of Zap70 during B cell development compromised negative selection of autoreactive B cells, resulting in pervasive autoantibody production. Strict segregation of the two kinases is critical for normal B cell selection and represents a central safeguard against the development of autoimmune disease and B cell malignancies.
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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.