https://scholars.lib.ntu.edu.tw/handle/123456789/160110
標題: | The Tumor Suppressor Death-Associated Protein Kinase Targets to Tcr- Stimulated Nf-Kappa B Activation | 作者: | CHUANG, YA-TING CHEN, RUEY-HWA LAI, MING-ZONG |
公開日期: | 2008 | 卷: | v.180 | 期: | n.5 | 起(迄)頁: | 3238-3249 | 來源出版物: | JOURNAL OF IMMUNOLOGY | 摘要: | Death-associated protein kinase (DAPK) is a unique multidomain kinase acting both as a tumor suppressor and an apoptosis inducer. The molecular mechanism underlying the effector function of DAPK is not fully understood , while the role of DAPK in T lymphocyte activation is mostly unknown. DAPK was activated after TCR stimulation. Through the expression of a dominant-negative and a constitutively active form of DAPK in T cells, we found that DAPK negatively regulated T cell activation. DAPK markedly affected T cell proliferation and IL-2 production. We identified TCR- induced NF-kappaB activation as a target of DAPK. In contrast, IL-1beta- and TNF-alpha-triggered NF- kappaB activation was not affected by DAPK. We further found that DAPK selectively modulated the TCR-induced translocation of protein kinase Ctheta, Bcl-10, and IkappaB kinase into membrane rafts. Notably, the effect of DAPK on the raft entry was specific for the NF-kappaB pathway, as other raft-associated molecules, such as linker for activation of T cells, were not affected. Our results clearly demonstrate that DAPK is a novel regulator targeted to TCR-activated NF- kappaB and T cell activation. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/174499 |
顯示於: | 分子醫學研究所 |
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