ArticleJournal of immunology (Baltimore, Md. : 1950)2012
A computational model for early events in B cell antigen receptor signaling: analysis of the roles of Lyn and Fyn.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
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- Tyrosine Protein Kinase SYK-Related Gene Signature in Baseline Immune Cells Associated with Adjuvant Immunotherapy-Induced Immune-Related Adverse Events in Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Catalyst: Fast and flexible modeling of reaction networks.PLoS computational biology · 2023Article
- Reduced IRF4 expression promotes lytic phenotype in Type 2 EBV-infected B cells.PLoS pathogens · 2022Article
- Modeling the Cluster Size Distribution of Vascular Endothelial Growth Factor (VEGF) Receptors.Bioinformatics and biology insights · 2022Article
- Fyn Kinase Activity and Its Role in Neurodegenerative Disease Pathology: a Potential Universal Target?Molecular neurobiology · 2021Review
- Antibody:CD47 ratio regulates macrophage phagocytosis through competitive receptor phosphorylation.Cell reports · 2021Article
- Review
- The multi-kinase inhibitor TG02 induces apoptosis and blocks B-cell receptor signaling in chronic lymphocytic leukemia through dual mechanisms of action.Blood cancer journal · 2021Article
- PAG1 directs SRC-family kinase intracellular localization to mediate receptor tyrosine kinase-induced differentiation.Molecular biology of the cell · 2020Article
- Constitutive Activation of the B Cell Receptor Underlies Dysfunctional Signaling in Chronic Lymphocytic Leukemia.Cell reports · 2019Article
- Sphingomyelin synthase 1 enhances BCR signaling to promote lupus-like autoimmune response.EBioMedicine · 2019Article
- Epstein-Barr virus microRNAs regulate B cell receptor signal transduction and lytic reactivation.PLoS pathogens · 2019Article
- An Overview of Network-Based and -Free Approaches for Stochastic Simulation of Biochemical Systems.Computation (Basel, Switzerland) · 2018Article
- A multiscale modeling study of particle size effects on the tissue penetration efficacy of drug-delivery nanoparticles.BMC systems biology · 2017Article
- Automated visualization of rule-based models.PLoS computational biology · 2017Article
- Effective Combination Therapies for B-cell Lymphoma Predicted by a Virtual Disease Model.Cancer research · 2017Article
- Mathematical Models for Immunology: Current State of the Art and Future Research Directions.Bulletin of mathematical biology · 2016Review
- Directed Evolution of a Highly Specific FN3 Monobody to the SH3 Domain of Human Lyn Tyrosine Kinase.PloS one · 2016Article
- Modeling for (physical) biologists: an introduction to the rule-based approach.Physical biology · 2015Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
BCR signaling regulates the activities and fates of B cells. BCR signaling encompasses two feedback loops emanating from Lyn and Fyn, which are Src family protein tyrosine kinases (SFKs). Positive feedback arises from SFK-mediated trans phosphorylation of BCR and receptor-bound Lyn and Fyn, which increases the kinase activities of Lyn and Fyn. Negative feedback arises from SFK-mediated cis phosphorylation of the transmembrane adapter protein PAG1, which recruits the cytosolic protein tyrosine kinase Csk to the plasma membrane, where it acts to decrease the kinase activities of Lyn and Fyn. To study the effects of the positive and negative feedback loops on the dynamical stability of BCR signaling and the relative contributions of Lyn and Fyn to BCR signaling, we consider in this study a rule-based model for early events in BCR signaling that encompasses membrane-proximal interactions of six proteins, as follows: BCR, Lyn, Fyn, Csk, PAG1, and Syk, a cytosolic protein tyrosine kinase that is activated as a result of SFK-mediated phosphorylation of BCR. The model is consistent with known effects of Lyn and Fyn deletions. We find that BCR signaling can generate a single pulse or oscillations of Syk activation depending on the strength of Ag signal and the relative levels of Lyn and Fyn. We also show that bistability can arise in Lyn- or Csk-deficient cells.
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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.