ArticleThe Journal of experimental medicine2000
Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 84 citations in OpenAlex.
- Cbl promotes MyD88 ubiquitin-mediated degradation in macrophages via phosphorylation and calcium mobilization.Frontiers in immunology · 2025Article
- BLNK negatively regulates innate antifungal immunity through inhibiting c-Cbl-mediated macrophage migration.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- IKAROS in Acute Leukemia: A Positive Influencer or a Mean Hater?International journal of molecular sciences · 2023Review
- Knockout of c-Cbl slows EGFR endocytic trafficking and enhances EGFR signaling despite incompletely blocking receptor ubiquitylation.Pharmacology research & perspectives · 2021Article
- Ikaros Proteins in Tumor: Current Perspectives and New Developments.Frontiers in molecular biosciences · 2021Review
- The regulators of BCR signaling during B cell activation.Blood science (Baltimore, Md.) · 2019Review
- Ubiquitin Ligases in Cancer Immunotherapy - Balancing Antitumor and Autoimmunity.Trends in molecular medicine · 2019Review
- Article
- Intracellular B Lymphocyte Signalling and the Regulation of Humoral Immunity and Autoimmunity.Clinical reviews in allergy & immunology · 2017Review
- The Ikaros family of zinc-finger proteins.Acta pharmaceutica Sinica. B · 2016Review
- Targeting B-cell receptor signaling in leukemia and lymphoma: how and why?International journal of hematologic oncology · 2016Review
- Modulation of Immune Cell Functions by the E3 Ligase Cbl-b.Frontiers in oncology · 2015Review
- The autoinhibitory C-terminal SH2 domain of phospholipase C-γ2 stabilizes B cell receptor signalosome assembly.Science signaling · 2014Article
- Recruitment of Cbl-b to B cell antigen receptor couples antigen recognition to Toll-like receptor 9 activation in late endosomes.PloS one · 2014Article
- The Syk-binding ubiquitin ligase c-Cbl mediates signaling-dependent B cell receptor ubiquitination and B cell receptor-mediated antigen processing and presentation.The Journal of biological chemistry · 2012Article
- Loss of Cbl-b increases osteoclast bone-resorbing activity and induces osteopenia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2009Article
- Control of the B cell-intrinsic tolerance programs by ubiquitin ligases Cbl and Cbl-b.Immunity · 2007Article
- Article
- c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses.The Biochemical journal · 2005Review
- ZAP-70 is expressed by a subset of normal human B-lymphocytes displaying an activated phenotype.Leukemia · 2005Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence indicates that the Cbl protein plays a negative role in immune receptor signaling; however, the mode of Cbl action in B cell receptor (BCR) signaling still remains unclear. DT40 B cells deficient in Cbl showed enhanced BCR-mediated phospholipase C (PLC)-gamma2 activation, thereby leading to increased apoptosis. A possible explanation for the involvement of Cbl in PLC-gamma2 activation was provided by findings that Cbl interacts via its Src homology 2 (SH2) domain with B cell linker protein (BLNK) after BCR ligation. BLNK is a critical adaptor molecule for PLC-gamma2 tyrosine phosphorylation through its binding to the PLC-gamma2 SH2 domains. As a consequence of the interaction between Cbl and BLNK, the BCR-induced recruitment of PLC-gamma2 to BLNK and the subsequent PLC-gamma2 tyrosine phosphorylation were inhibited. Thus, our data suggest that Cbl negatively regulates the PLC-gamma2 pathway by inhibiting the association of PLC-gamma2 with BLNK.
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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.