T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression. Author Jeroen Roose, Maximilian Diehn, Michael Tomlinson, Joseph Lin, Ash Alizadeh, David Botstein, Patrick Brown, Arthur Weiss Publication Year 2003 Type Journal Article 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. Keywords Animals, Blotting, Western, Extracellular Signal-Regulated MAP Kinases, Immunoprecipitation, Signal Transduction, Gene Expression Regulation, Mice, Molecular Sequence Data, Transcription, Genetic, Humans, Models, Biological, Multigene Family, Oligonucleotide Array Sequence Analysis, Adaptor Proteins, Signal Transducing, DNA-Binding Proteins, Homeodomain Proteins, Phosphoproteins, Ligands, RNA, B-Lymphocytes, Benzamides, Blotting, Northern, Cell Separation, DNA, Complementary, Enzyme Activation, Flow Cytometry, Jurkat Cells, MAP Kinase Signaling System, Phosphorylation, Piperazines, Protein Kinase C, Proto-Oncogene Proteins c-abl, Pyrimidines, Receptors, Antigen, T-Cell, Thymus Gland, Tyrosine Journal PLoS Biol Volume 1 Issue 2 Pages E53 Date Published 11/2003 Alternate Journal PLoS Biol. Google ScholarBibTeXEndNote X3 XML