ArticleMolecular and cellular biology2007
PAG-associated FynT regulates calcium signaling and promotes anergy in T lymphocytes.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 87 citations in OpenAlex.
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- The miRNA and PD-1/PD-L1 signaling axis: an arsenal of immunotherapeutic targets against lung cancer.Cell death discovery · 2024Review
- Surface Immune Checkpoints as Potential Biomarkers in Physiological Pregnancy and Recurrent Pregnancy Loss.International journal of molecular sciences · 2024Article
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- Novel Immune Checkpoints in Esophageal Cancer: From Biomarkers to Therapeutic Targets.Frontiers in immunology · 2022Review
- Expression profiling of mRNA and functional network analyses of genes regulated by human papilloma virus E6 and E7 proteins in HaCaT cells.Frontiers in microbiology · 2022Article
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- TIM-3 in normal and malignant hematopoiesis: Structure, function, and signaling pathways.Cancer science · 2021Review
- The TIM3/Gal9 signaling pathway: An emerging target for cancer immunotherapy.Cancer letters · 2021Article
- Naturally Occurring Genetic Alterations in Proximal TCR Signaling and Implications for Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity.Frontiers in physiology · 2021Article
- Cellular and Molecular Mechanisms of CD8International journal of molecular sciences · 2020Review
- Expression Analysis of Fyn and Bat3 Signal Transduction Molecules in Patients with Chronic Lymphocytic Leukemia.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Targeting novel inhibitory receptors in cancer immunotherapy.Seminars in immunology · 2020Review
- Resistance to Checkpoint Inhibition in Cancer Immunotherapy.Translational oncology · 2020Review
- Targeting Checkpoint Receptors and Molecules for Therapeutic Modulation of Natural Killer Cells.Frontiers in immunology · 2018Review
- Adaptive NKG2CFrontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphoprotein associated with glycolipid-enriched membranes (PAG), also named Csk-binding protein (Cbp), is a transmembrane adaptor associated with lipid rafts. It is phosphorylated on multiple tyrosines located in the cytoplasmic domain. One tyrosine, tyrosine 314 (Y314) in the mouse, interacts with Csk, a protein tyrosine kinase that negatively regulates Src kinases. This interaction enables PAG to inhibit T-cell antigen receptor (TCR)-mediated T-cell activation. PAG also associates with the Src-related kinase FynT. Genetic studies indicated that FynT was required for PAG tyrosine phosphorylation and binding of PAG to Csk in T cells. Herein, we investigated the function and regulation of PAG-associated FynT. Our data showed that PAG was constitutively associated with FynT in unstimulated T cells and that this association was rapidly lost in response to TCR stimulation. Dissociation of the PAG-FynT complex preceded PAG dephosphorylation and PAG-Csk dissociation after TCR engagement. Interestingly, in anergic T cells, the association of PAG with FynT, but not Csk, was increased. Analyses of PAG mutants provided evidence that PAG interacted with FynT by way of tyrosines other than Y314. Enforced expression of a PAG variant interacting with FynT, but not Csk, caused a selective enhancement of TCR-triggered calcium fluxes in normal T cells. Furthermore, it promoted T-cell anergy. Both effects were absent in mice lacking FynT, implying that the effects were mediated by PAG-associated FynT. Hence, besides enabling PAG tyrosine phosphorylation and the PAG-Csk interaction, PAG-associated FynT can stimulate calcium signals and favor T-cell anergy. These data improve our comprehension of the function of PAG in T cells. They also further implicate FynT in T-cell anergy.
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