Gene regulation mediated by calcium signals in strongTstrong lymphocytes.pdfVIP

© 2001 Nature Publishing Group ARTICLES Gene regulation mediated by calcium signals in T lymphocytes 1 2 3 2 1 Stefan Feske , Jena Giltnane , Ricardo Dolmetsch , Louis M. Staudt and Anjana Rao m o Modulation of many signaling pathways in antigen-stimulated T and B cells results in global changes c . e in gene expression. Here we investigate the contribution of calcium signaling to gene expression in T r u t cells using cell lines from two severe-combined immunodeficiency patients with several cytokine a n . l deficiencies and diminished activation of the transcription factor NFAT nuclear factor of activated T o n u cells. These T cells show a strong defect in transmembrane calcium influx that is also apparent in m m their B cells and fibroblasts. DNA microarray analysis of calcium entry–deficient and control T cells i / / 2+ : shows that Ca signals both activate and repress gene expression and are largely transduced through p t t the phosphatase calcineurin. We demonstrate an elaborate network of signaling pathways h p downstream of the T cell receptor, explaining the complexity of changes in gene expression during T u o r cell activation. G g n i h s i Calcium plays an essential role in lymphocyte activation and matura- cellular stimulation it is dephosphorylated by the calcium-dependent l b u tion. Cross-linking of antigen or Fc receptors on T cells, B cells, mast phosphatase calcineurin, whereupon it translocates to the nucleus and P