ArticlePLoS biology2003
T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression.
Article in PLoS biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 99 citations in OpenAlex.
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- Tonic Signals: Why Do Lymphocytes Bother?Trends in immunology · 2017Review
- ArtinM Mediates Murine T Cell Activation and Induces Cell Death in Jurkat Human Leukemic T Cells.International journal of molecular sciences · 2017Article
- Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells.Cell reports · 2017Article
- Phorbol ester-mediated re-expression of endogenous LAT adapter in J.CaM2 cells: a model for dissecting drivers and blockers of LAT transcription.Genes and immunity · 2016Article
- A CRISPR-Based Toolbox for Studying T Cell Signal Transduction.BioMed research international · 2016Article
- Recent insights into the transcriptional control of the Tcra/Tcrd locus by distant enhancers during the development of T-lymphocytes.Transcription · 2015Review
- Receptor revision in CD4 T cells is influenced by follicular helper T cell formation and germinal-center interactions.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Coincidence detection of antibodies and interferon for sensing microbial context.Nature immunology · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Signal transduction pathways guided by cellular receptors commonly exhibit low-level constitutive signaling in a continuous, ligand-independent manner. The dynamic equilibrium of positive and negative regulators establishes such a tonic signal. Ligand-independent signaling by the precursors of mature antigen receptors regulates development of B and T lymphocytes. Here we describe a basal signal that controls gene expression profiles in the Jurkat T cell line and mouse thymocytes. Using DNA microarrays and Northern blots to analyze unstimulated cells, we demonstrate that expression of a cluster of genes, including RAG-1 and RAG-2, is repressed by constitutive signals requiring the adapter molecules LAT and SLP-76. This TCR-like pathway results in constitutive low-level activity of Erk and Abl kinases. Inhibition of Abl by the drug STI-571 or inhibition of signaling events upstream of Erk increases RAG-1 expression. Our data suggest that physiologic gene expression programs depend upon tonic activity of signaling pathways independent of receptor ligation.
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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.