ArticlePloS one2011
Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRα gene expression.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFα inhibitors.Arthritis research & therapy · 2015Trial
- Irradiated umbilical cord mesenchymal stem cell-coated high oxygen-permeable hydrogel lenses inhibit corneal inflammation and neovascularization after corneal alkali burns.Scientific reports · 2025Article
- Stress-Induced Immunosuppression Inhibits Regional Immune Responses in Chicken Adipose Tissue Partially through Suppressing T Cells by Up-Regulating Steroid Metabolism.Animals : an open access journal from MDPI · 2024Article
- Defective LAT signalosome pathology in mice mimics human IgG4-related disease at single-cell level.The Journal of experimental medicine · 2023Article
- A Novel, LAT/Lck Double Deficient T Cell Subline J.CaM1.7 for Combined Analysis of Early TCR Signaling.Cells · 2021Article
- The Clinical Aspect of Adaptor Molecules in T Cell Signaling: Lessons Learnt From Inborn Errors of Immunity.Frontiers in immunology · 2021Review
- Strength of tonic T cell receptor signaling instructs T follicular helper cell-fate decisions.Nature immunology · 2020Article
- mTOR and other effector kinase signals that impact T cell function and activity.Immunological reviews · 2019Review
- Alternative ZAP70-p38 signals prime a classical p38 pathway through LAT and SOS to support regulatory T cell differentiation.Science signaling · 2019Article
- Active Tonic mTORC1 Signals Shape Baseline Translation in Naive T Cells.Cell reports · 2019Article
- Differential Regulation of Gene Expression in Lung Cancer Cells by Diacyglycerol-Lactones and a Phorbol Ester Via Selective Activation of Protein Kinase C Isozymes.Scientific reports · 2019Article
- Strategies to Address Chimeric Antigen Receptor Tonic Signaling.Molecular cancer therapeutics · 2018Review
- Tuning T Cell Signaling Sensitivity Alters the Behavior of CD4Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Tonic Signals: Why Do Lymphocytes Bother?Trends in immunology · 2017Review
- Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells.Cell reports · 2017Article
- The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway.Science signaling · 2015Article
- T-cell receptor α enhancer is inactivated in αβ T lymphocytes.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Recent insights into the transcriptional control of the Tcra/Tcrd locus by distant enhancers during the development of T-lymphocytes.Transcription · 2015Review
- Article
- Regulation of ras exchange factors and cellular localization of ras activation by lipid messengers in T cells.Frontiers in immunology · 2013Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
In contrast to the well-characterized T cell receptor (TCR) signaling pathways that induce genes that drive T cell development or polarization of naïve CD4 T cells into the diverse T(H)1, T(H)2, T(H)17 and T(reg) lineages, it is unclear what signals maintain specific gene expression in mature resting T cells. Resting T cells residing in peripheral lymphoid organs exhibit low-level constitutive signaling. Whereas tonic signals in B cells are known to be critical for survival, the roles of tonic signals in peripheral T cells are unknown. Here we demonstrate that constitutive signals in Jurkat T cell lines are transduced via the adapter molecule LAT and the Ras exchange factor RasGRP1 to maintain expression of TCRα mRNA and surface expression of the TCR/CD3 complex. Independent approaches of reducing basal activity through the LAT-diacylglycerol-RasGRP pathway led to reduced constitutive Ras-MEK-ERK signals and decreased TCRα mRNA and surface TCR expression in Jurkat cells. However, loss of TCR expression takes several days in these cell line experiments. In agreement with these in vitro approaches, inducible deletion of Lat in vivo results in reduced TCRα mRNA- and surface TCR-expression in a delayed temporal manner as well. Lastly, we demonstrate that loss of basal LAT-RasGRP signals appears to lead to silencing or repression of TCRα transcription. We postulate that basal LAT-diacylglycerol-RasGRP signals fulfill a regulatory function in peripheral T lymphocytes by maintaining proper gene expression programs.
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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.