<p>Antigenic stimulation of T lymphocytes initiates a complex series ofintracellular signal transduction pathways that leads to the expression of apanel of immunoregulatory genes, whose function is critical to theinitiation and coordination of the immune response. The multi-subunitnuclear factor of activated T cells (NFAT) transcription factor familyplays a pivotal role in this process and is involved in the expression of anumber of immunologically important genes. These include the cytokines IL-2,IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor, andtumour necrosis factor-alpha, as well as several cell-surface molecules,such as CD40L and FasL. Although originally described in T cells, it is nowapparent that NFAT proteins are also expressed in other immune system cells,including B cells, mast cells, basophils and natural killer cells, as wellas in a variety of non-immune cell types and tissues, such as skeletalmuscle, neurons, heart and adipocytes. However, although NFAT acts as acalcium-dependent transcription factor and serves to couple gene expressionto changes in intracellular calcium levels in most cases, NFAT target geneshave not been identified in these latter cell types.</p><p>NFAT proteins appear to be regulated primarily at the level of theirsubcellular localisation [<cite idref="PUB00011687"/>]. They are found exclusively in the cytoplasm ofresting T cells, and consist of 2 components: a pre-existing cytoplasmiccomponent that translocates into the nucleus on calcium mobilisation, and aninducible nuclear component comprising members of the activating protein-1(AP-1) family of transcription factors. In response to antigen receptorsignalling, the calcium-regulated phosphatase calcineurin acts directly todephosphorylate NFAT proteins, causing their rapid translocation from thecytoplasm to the nucleus, where they cooperatively bind their target</p> Nuclear factor of activated T cells (NFAT)