作者
Rishu Guo, Chi-Keung Wan, Jeffery H Carpenter, Talal Mousallem, Rose-Mary N Boustany, Chien-Tsun Kuan, A Wesley Burks, Xiao-Ping Zhong
发表日期
2008/8/19
期刊
Proceedings of the National Academy of Sciences
卷号
105
期号
33
页码范围
11909-11914
出版商
National Academy of Sciences
简介
Diacylglycerol (DAG) kinases (DGKs) are a family of enzymes that convert DAG to phosphatidic acid (PA), the physiologic functions of which have been poorly defined. We report here that DGK α and ζ synergistically promote T cell maturation in the thymus. Absence of both DGKα and ζ (DGKα−/−ζ−/−) results in a severe decrease in the number of CD4+CD8− and CD4−CD8+ single-positive thymocytes correlating with increased DAG-mediated signaling. Positive selection, but not negative selection, is impaired in DGKα−/−ζ−/− mice. The developmental blockage in DGKα−/−ζ−/− mice can be partially overcome by treatment with PA. Furthermore, decreased DGK activity also promotes thymic lymphomagenesis accompanying elevated Ras and Erk1/2 activation. Our data demonstrate a synergistic and critical role of DGK isoforms in T cell development and tumor suppression, and indicate that DGKs not only terminate …
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R Guo, CK Wan, JH Carpenter, T Mousallem… - Proceedings of the National Academy of Sciences, 2008