Study of the signaling pathway in TRAIL-induced T cell activation by yeast-two-hybrid system
Date Issued
2005
Date
2005
Author(s)
Hwang, Chuan-Hsiung
DOI
en-US
Abstract
Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL), a type Ⅱ transmembrane protein, is one of several members of the TNF superfamily that induces apoptosis through engagement of death receptors. TRAIL exists mainly in membrane-bound form, and its expression on T cells is induced after T cell activation by anti-CD3 or type I interferon (IFN). There is growing evidence that ligands of the TNF family, such as CD40L; CD30L; FasL, and TRANCE, transduced signals after engagement with their receptors. Our previous study has demonstrated that TRAIL stimulated with immobilized DR4, in conjunction with suboptimal immobilized anti-CD3, induced T cell proliferation and enhanced IFN-γ production. This indicates that in addition to direct triggering apoptosis through death receptor, TRAIL can tranduce reverse signals to induce T cell activation. However, the reverse signaling pathways transduced by TRAIL is still unclear. In our previous study, we found that p38 MAPK and PI3K/Akt activation was detected after TRAIL-induced T cell activation, indicating that p38 MAPK and PI3K/Akt pathway is involved in TRAIL reverse signaling pathway. It has been demonstrated that the NF-κB signaling pathway was involved in CD28 costimulation signaling pathway, suggesting that NF-κB signaling pathway is critical in costimulation of T cells. In this study, we use yeast-two-hybrid system to identify the possible molecules associated with TRAIL intracytoplasmic domain to transduce signal. Our results showed that JAK1 may be an associated protein in the cytoplasmic region of TRAIL and modulate the signaling transduction of TRAIL-induced T cell proliferation and IFN-γ production. Furthermore, the effect of TRAIL-induced T cell proliferation and IFN-γ production can be significantly blocked by JAK inhibitor, indicating JAK-STAT pathway is critical in TRAIL-induced T cell activation. Moreover, we also demonstrated that NF-κB pathway is activated during TRAIL-induced costimulation of T cells.
Subjects
酵母菌雙雜合系統
細胞活化
訊息傳導
yeast-two-hybrid system
T cell activation
signal transduction
TRAIL
Type
other
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