@article{1580,
  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},
  author = {Jeroen Roose and Maximilian Diehn and Michael Tomlinson and Joseph Lin and Ash Alizadeh and David Botstein and Patrick Brown and Arthur Weiss},
  title = {T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression.},
  abstract = {<p>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.</p>},
  year = {2003},
  journal = {PLoS Biol},
  volume = {1},
  pages = {E53},
  month = {11/2003},
  language = {eng},
}