T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression

Research output: Contribution to journalArticlepeer-review

Authors

  • JP Roose
  • M Diehn
  • J Lin
  • AA Alizadeh
  • PO Brown
  • D Botstein
  • A Weiss

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)271-287
Number of pages17
JournalPLoS Biology
Volume1
Issue number2
Publication statusPublished - 17 Nov 2003