ArticleScience signaling2013
Monovalent and multivalent ligation of the B cell receptor exhibit differential dependence upon Syk and Src family kinases.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 4 citations in OpenAlex.
- Virus-like antigen display delivers a stand-alone danger signal through the BCR that circumvents tolerance.bioRxiv : the preprint server for biology · 2026Article
- Immunoglobulin divalence promotes B-cell antigen receptor cluster scale-dependent functions.Cellular & molecular immunology · 2025Article
- SYK negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Towards a unifying model for B-cell receptor triggering.Nature reviews. Immunology · 2025Review
- 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
- Biomaterials-mediated ligation of immune cell surface receptors for immunoengineering.Immuno-oncology technology · 2024Review
- Effect of Antigen Valency on Autoreactive B-Cell Targeting.Molecular pharmaceutics · 2024Article
- A universal design of restructured dimer antigens: Development of a superior vaccine against the paramyxovirus in transgenic rice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The ion channel TRPV5 regulates B-cell signaling and activation.Frontiers in immunology · 2024Article
- Antigen footprint governs activation of the B cell receptor.Nature communications · 2023Article
- A Novel TLR4-SYK Interaction Axis Plays an Essential Role in the Innate Immunity Response in Bovine Mammary Epithelial Cells.Biomedicines · 2022Article
- Docking of Syk to FcεRI is enhanced by Lyn but limited in duration by SHIP1.Molecular biology of the cell · 2022Article
- ZAP70, too little, too much can lead to autoimmunity.Immunological reviews · 2022Review
- Differences in the dynamics of the tandem-SH2 modules of the Syk and ZAP-70 tyrosine kinases.Protein science : a publication of the Protein Society · 2021Article
- Acute Csk inhibition hinders B cell activation by constraining the PI3 kinase pathway.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Mechanisms determining a differential threshold for sensing Src family kinase activity by B and T cell antigen receptors.The Journal of biological chemistry · 2020Article
- Role of nanoscale antigen organization on B-cell activation probed using DNA origami.Nature nanotechnology · 2020Article
- Control of Platelet CLEC-2-Mediated Activation by Receptor Clustering and Tyrosine Kinase Signaling.Biophysical journal · 2020Article
- Article
- Constitutive Activation of the B Cell Receptor Underlies Dysfunctional Signaling in Chronic Lymphocytic Leukemia.Cell reports · 2019Article
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11 authors at 4 institutions in 1 country.
Funding
Abstract
The Src and Syk families of kinases are two distinct sets of kinases that play critical roles in initiating membrane-proximal B cell receptor (BCR) signaling. However, unlike in other lymphocytes, such as T cells, the "division of labor" between Src family kinases (SFKs) and Syk in B cells is not well separated because both Syk and SFKs can phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) present in proteins comprising the BCR. To understand why B cells require both SFKs and Syk for activation, we investigated the roles of both families of kinases in BCR signaling with computational modeling and in vitro experiments. Our computational model suggested that positive feedback enabled Syk to substantially compensate for the absence of SFKs when spatial clustering of BCRs was induced by multimeric ligands. We confirmed this prediction experimentally. In contrast, when B cells were stimulated by monomeric ligands that failed to produce BCR clustering, both Syk and SFKs were required for complete and rapid BCR activation. Our data suggest that SFKs could play a pivotal role in increasing BCR sensitivity to monomeric antigens of pathogens and in mediating a rapid response to soluble multimeric antigens of pathogens that can induce spatial BCR clustering.
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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.