ArticleThe Journal of experimental medicine2003
Cbl-b negatively regulates B cell antigen receptor signaling in mature B cells through ubiquitination of the tyrosine kinase Syk.
Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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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.
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Who cites it
62 citing papers in PubMed, 138 citations in OpenAlex.
- Non-receptor tyrosine kinase c-Abl downstream of C-type lectin receptors regulates innate antifungal immunity through c-Cbl/MAPK pathway.Infection and immunity · 2026Article
- Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and function.Nature immunology · 2026Article
- Phosphorylation at Y317 on Syk negatively regulates both ITAM- and hemITAM-mediated signaling and function in platelets.Blood advances · 2025Article
- Cbl-b inhibitor NX-1607 activates MAPK/ERK signaling pathway and enhances T-cell activation.Journal for immunotherapy of cancer · 2025Article
- The Role of Ubiquitin-Proteasome System (UPS) in Asthma Pathology.Journal of asthma and allergy · 2025Review
- Single-cell mRNA analysis and surface marker expression profiling of circulating immune cells in humans with alpha-gal syndrome.Frontiers in immunology · 2025Article
- Inhibition of Cbl-b restores effector functions of human intratumoral NK cells.Journal for immunotherapy of cancer · 2024Article
- Innate immune signal transduction pathways to fungal infection: Components and regulation.Cell insight · 2024Review
- B cell responses to membrane-presented antigens require the function of the mechanosensitive cation channel Piezo1.Science signaling · 2023Article
- E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation.Viruses · 2023Review
- Retinopathy as an initial sign of hereditary immunological diseases: report of six families and challenges in eye clinic.Frontiers in immunology · 2023Article
- Human T-bet+ B cell development is associated with BTK activity and suppressed by evobrutinib.JCI insight · 2022Article
- Tumor rejection inJournal for immunotherapy of cancer · 2021Article
- Article
- Transcriptional regulation of memory B cell differentiation.Nature reviews. Immunology · 2021Review
- E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy.Clinical and experimental immunology · 2021Review
- Syk degradation restrains plasma cell formation and promotes zonal transitions in germinal centers.The Journal of experimental medicine · 2020Article
- The regulators of BCR signaling during B cell activation.Blood science (Baltimore, Md.) · 2019Review
- Article
- Regulation of immune responses by E3 ubiquitin ligase Cbl-b.Cellular immunology · 2019Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Members of the Cbl family of molecular adaptors play key roles in regulating tyrosine kinase-dependent signaling in a variety of cellular systems. Here we provide evidence that in B cells Cbl-b functions as a negative regulator of B cell antigen receptor (BCR) signaling during the normal course of a response. In B cells from Cbl-b-deficient mice cross-linking the BCRs resulted in sustained phosphorylation of Igalpha, Syk, and phospholipase C (PLC)-gamma2, leading to prolonged Ca2+ mobilization, and increases in extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal protein kinase (JNK) phosphorylation and surface expression of the activation marker, CD69. Image analysis following BCR cross-linking showed sustained polarization of the BCRs into large signaling-active caps associated with phosphorylated Syk in Cbl-b-deficient B cells in contrast to the BCRs in Cbl-b-expressing B cells that rapidly proceeded to form small, condensed, signaling inactive caps. Significantly, prolonged phosphorylation of Syk correlated with reduced ubiquitination of Syk indicating that Cbl-b negatively regulates BCR signaling by targeting Syk for ubiquitination.
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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.