ATM在 T細胞活化中角色之研究
Study on the Role of ATM in T Cell Activation
Date Issued
2006
Date
2006
Author(s)
Lee, Chin-Nien
DOI
zh-TW
Abstract
The Ataxia-Telangiectasia Mutated (ATM) protein kinase, mutations of which are associated with the human disease ataxia-telangiectasia (A-T), mediates responses to DNA damage in mammalian cells. A-T patients and Atm-deficient mice display neurologic dysfunction, defects in T lymphocyte maturation, cancer predisposition and radiation sensitivity. Recent study showed ATM protects bone marrow hemotapoietic stem cells (HSC) from oxidative stress and is required for sustained adult lymphopoiesis. Moreover, ATM routine surveillance of intermediates in V(D)J recombination, which is essential for TCR rearrangement. However, the role of ATM in mature T cells function is still unclear recently. Some reports showed that stimulation of T cells by using PHA, EGF or superantigen is able to alter ATM protein or gene expression level to some extent. Therefore, a general hypothesis emerges that ATM is involved in regulation of T cell activation. To test this hypothesis, we used lentiviral shRNA system to knockdown endogenous ATM in Jurkat T cells.
Downregulation of ATM in Jurkat T cell cause dramatically increase in IL-2 production after stimulated with either OKT-3 plus anti-CD28 or SEE superantigen. To further study the molecular mechanisms, we found a partial effect on PKC-theta activation at early time point. However, the nuclear translocation of NFkB is not affected. LAT, Akt, ERK and calcium-related signals show no significant difference. Moreover, there is no change either in ATM protein expression level or ATM Ser1981 phosphorylation during T cell activation. In summary, knockdown ATM partially activate PKC-theta upon short-term stimulation, but the detail mechanisms are still unclear. This study provides information other than respondses to DNA damage, ATM may play a suppresive role in T cell activation, but the regulatory mechanism need to be clarified extensively.
Subjects
ATM
Ataxia Telangiectasia Mutated
Ataxia Telangiectasia
T細胞活化
TCR訊息傳遞
T cell activation
TCR signal transduction
SDGs
Type
other
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