ArticleThe Journal of biological chemistry2011
A new pathway of CD5 glycoprotein-mediated T cell inhibition dependent on inhibitory phosphorylation of Fyn kinase.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 44 citations in OpenAlex.
- Persistent antigen is essential for sustainingScience advances · 2026Article
- The CD6 interactome orchestrates ligand-independent T cell inhibitory signaling.Cell communication and signaling : CCS · 2024Article
- FYN: emerging biological roles and potential therapeutic targets in cancer.Journal of translational medicine · 2023Review
- The perception and response of T cells to a changing environment are based on the law of initial value.Science signaling · 2022Review
- Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2020Review
- CD5 dynamically calibrates basal NF-κB signaling in T cells during thymic development and peripheral activation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Domain-specific CD6 monoclonal antibodies identify CD6 isoforms generated by alternative-splicing.Immunology · 2019Article
- 2B4 costimulatory domain enhancing cytotoxic ability of anti-CD5 chimeric antigen receptor engineered natural killer cells against T cell malignancies.Journal of hematology & oncology · 2019Article
- Chimeric Antigen Receptors for T-Cell Malignancies.Frontiers in oncology · 2019Review
- Strategies to Address Chimeric Antigen Receptor Tonic Signaling.Molecular cancer therapeutics · 2018Review
- CD6, a Rheostat-Type Signalosome That Tunes T Cell Activation.Frontiers in immunology · 2018Review
- CD5, an Undercover Regulator of TCR Signaling.Frontiers in immunology · 2018Review
- Co-recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD5 as a key regulator of TCR-induced ubiquitylation.Molecular systems biology · 2016Article
- CD5 expression is regulated during human T-cell activation by alternative polyadenylation, PTBP1, and miR-204.European journal of immunology · 2016Article
- A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies.Blood · 2015Article
- Structures of CD6 and Its Ligand CD166 Give Insight into Their Interaction.Structure (London, England : 1993) · 2015Article
- Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries.Oncotarget · 2015Article
- PAG--a multipurpose transmembrane adaptor protein.Oncogene · 2014Review
- T-cell modulatory properties of CD5 and its role in antitumor immune responses.Oncoimmunology · 2013Article
- Functional avidity: a measure to predict the efficacy of effector T cells?Clinical & developmental immunology · 2012Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Triggering of the T cell receptor initiates a signaling cascade resulting in the activation of the T cell. These signals are integrated alongside those resulting from the triggering of other receptors whose function is to modulate the overall response. CD5 is an immunotyrosine-based inhibition motif-bearing receptor that antagonizes the overt T cell receptor activation response by recruiting inhibitory intracellular mediators such as SHP-1, RasGAP, or Cbl. We now propose that the inhibitory effects of CD5 are also mediated by a parallel pathway that functions at the level of inhibition of Fyn, a kinase generally associated with T cell receptor-mediated activation. After CD5 ligation, phosphorylation of the negative regulatory tyrosine (Tyr(531)) of Fyn increases, and this correlates with a substantial reduction in the kinase activity of Fyn and a profound inhibition of ZAP-70 activation. The effect requires the last 23 amino acids of the cytoplasmic domain of the receptor, strongly implying the involvement of a new CD5-interacting signaling or adaptor protein. Furthermore, we show that upon CD5 ligation there is a profound shift in its distribution from the bulk fluid phase to the lipid raft environment, where it associates with Fyn, Lck, and PAG. We suggest that the relocation of CD5, which we also show is capable of forming homodimers, to the proximity of raft-resident molecules enables CD5 to inhibit membrane proximal signaling by controlling the phosphorylation and activity of Fyn, possibly by interfering with the disassembly of C-terminal Src kinase (Csk)-PAG-Fyn complexes during T cell activation.
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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.