T cell Basal Signaling

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. Ligandindependent signaling by the precursors of mature antigen receptors regulates development of B- and T-lymphocytes. Here we describe a basal signal controlling 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 RAG2, is repressed by constitutive signals requiring the adapter molecules LAT and SLP-76. This TCR-like pathway results from constitutive low-level activity of Erk and Abl kinases. Inhibition of Abl by the drug STI-571 or 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. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set Using regression correlation