Format

Send to

Choose Destination
PLoS Biol. 2003 Nov;1(2):E53. Epub 2003 Nov 17.

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

Author information

1
Department of Medicine, University of California, San Francisco, USA.

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.

PMID:
14624253
PMCID:
PMC261890
DOI:
10.1371/journal.pbio.0000053
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have declared that no conflicts of interest exist.

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center