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

Authors
 Hyoung-Pyo Kim  ;  Byung-Gyu Kim  ;  Warren J. Leonard  ;  John Letterio 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.280(40) : 34042-34047, 2005 
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
 0021-9258 
Issue Date
2005
MeSH
Animals ; Binding Sites ; CD4-Positive T-Lymphocytes/physiology ; Gene Expression Regulation* ; Interleukin-2 Receptor alpha Subunit ; Mice ; Mice, Inbred C57BL ; Receptors, Interleukin/biosynthesis* ; Receptors, Interleukin/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Smad Proteins/physiology* ; T-Lymphocytes/physiology ; Transforming Growth Factor beta/physiology*
Keywords
16087671
Abstract
The interleukin 2 receptor alpha chain (IL-2Ralpha) 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-2Ralpha induction in response to antigen and IL-2. We now show that TGF-beta cooperates with T cell receptor (TCR) signaling to increase IL-2Ralpha gene expression. Moreover, we identify a sixth positive regulatory region that regulates IL-2Ralpha expression in cells treated with anti-CD3 + anti-CD28 as well as TGF-beta 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-2Ralpha induction by TGF-beta in CD4+ T cells from both Smad3-/- and Smad4-/- mice. Thus, we have identified a novel positive regulatory region in the IL-2Ralpha gene that mediates TGF-beta-dependent induction of the gene. These findings have implications related to IL-2Ralpha expression on activated T cells and regulatory T cells.
Files in This Item:
T200504625.pdf Download
DOI
10.1074/jbc.M505833200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114965
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