| Primary Identifier | IPR008366 | Type | Family |
| Short Name | NFAT |
| description | 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.NFAT proteins appear to be regulated primarily at the level of theirsubcellular localisation []. 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 |
