https://scholars.lib.ntu.edu.tw/handle/123456789/160860
標題: | Lipid Raft Assembly and Lck Recruitment in Trail Costimulation Mediates Nf - B Activation and T Cell Proliferation | 作者: | CHIA, HUANG SHIH TSAI, HWEI-FANG TZENG, HORNG-TAY LIAO, HSIU-JUNG HSU, PING-NING |
公開日期: | 2011 | 卷: | v.186 | 期: | n.2 | 起(迄)頁: | 931-939 | 來源出版物: | JOURNAL OF IMMUNOLOGY | 摘要: | The TNF-related apoptosis-inducing ligand was shown to provide a costimulatory signal that cooperates with the TCR/ CD3 complex to induce T cell proliferation and cytokine production. Although a number of signaling pathways were linked to the TCR/CD3 complex, it is not known how these two receptors cooperate to induce T cell activation. In this study, we show that TRAIL-induced costimulation of T cells depends on activation of the NF- B pathway. TRAIL induced the NF- B pathway by phosphorylation of inhibitor of B factor kinase and protein kinase C in conjunction with anti-CD3. Furthermore, we demonstrated that TRAIL costimulation induced phosphorylation of the upstream TCR- proximal tyrosine kinases, Lck and ZAP70. Ligation of the TRAIL by its soluble receptor, DR4-Fc, alone was able to induce the phosphorylation of Lck and ZAP70 and to activate the NF- B pathway; however, it was insufficient to fully activate T cells to support T cell proliferation. In contrast, TRAIL engagement in conjunction with anti-CD3, but not TRAIL ligation alone, induced lipid raft assembly and recruitment of Lck and PKC . These results demonstrate that TRAIL costimulation mediates NF- B activation and T cell proliferation by lipid raft assembly and recruitment of Lck. Our results suggest that in TRAIL costimulation, lipid raft recruitment of Lck integrates mitogenic NF- B–dependent signals from the TCR and TRAIL in T lymphocytes. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/240945 |
顯示於: | 免疫學研究所 |
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