Smad-dependent Cooperative Regulation of Interleukin 2 Receptor α Chain Gene Expression by T Cell Receptor and Transforming Growth Factor-β

Hyoung-Pyo Kim, Byung-Gyu Kim, John Letterio, Warren J. Leonard
2005 Journal of Biological Chemistry  
The interleukin 2 receptor ␣ chain (IL-2R␣) is a component of high affinity IL-2 receptors and thus critically regulates T cell growth and other lymphoid functions. Five positive regulatory regions together control lineage-restricted and activation-dependent IL-2R␣ induction in response to antigen and IL-2. We now show that TGF-␤ cooperates with T cell receptor (TCR) signaling to increase IL-2R␣ gene expression. Moreover, we identify a sixth positive regulatory region that regulates IL-2R␣
more » ... ssion in cells treated with anti-CD3 ؉ anti-CD28 as well as TGF-␤ and show that this region contains binding sites for Smad3, AP-1, and cAMP-responsive element-binding protein/ATF proteins. The importance of Smad complexes is indicated by impaired IL-2R␣ induction by TGF-␤ in CD4 ؉ T cells from both Smad3 ؊/؊ and Smad4 ؊/؊ mice. Thus, we have identified a novel positive regulatory region in the IL-2R␣ gene that mediates TGF-␤-dependent induction of the gene. These findings have implications related to IL-2R␣ expression on activated T cells and regulatory T cells.
doi:10.1074/jbc.m505833200 pmid:16087671 fatcat:afqp6eh3u5ad3ayd53hh2uiqri