|Title||T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression.|
|Publication Type||Journal Article|
|Year of Publication||2003|
|Authors||Roose, JP, Diehn, M, Tomlinson, MG, Lin, J, Alizadeh, AA, Botstein, D, Brown, PO, Weiss, A|
|Date Published||2003 Nov|
|Keywords||Adaptor Proteins, Signal Transducing, Animals, B-Lymphocytes, Benzamides, Blotting, Northern, Blotting, Western, Cell Separation, DNA, Complementary, DNA-Binding Proteins, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Flow Cytometry, Gene Expression Regulation, Homeodomain Proteins, Humans, Immunoprecipitation, Jurkat Cells, Ligands, MAP Kinase Signaling System, Mice, Models, Biological, Molecular Sequence Data, Multigene Family, Oligonucleotide Array Sequence Analysis, Phosphoproteins, Phosphorylation, Piperazines, Protein Kinase C, Proto-Oncogene Proteins c-abl, Pyrimidines, Receptors, Antigen, T-Cell, RNA, Signal Transduction, Thymus Gland, Transcription, Genetic, Tyrosine|
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.
|Alternate Journal||PLoS Biol.|