Rap1在T細胞活化上所扮演的角色
The Role of the Small G Protein Rap1 in T cell Activation
Date Issued
2004
Date
2004
Author(s)
Tsou, Wen-I
DOI
zh-TW
Abstract
Rap1 is activated by TCR signaling and is participated in integrin activation. The exact role of Rap1 in T cell activation and the mechanism on how Rap1 regulates integrin activation have not been precisely defined. In this study, we explored the role of Rap1 in three different aspects. First, we examined the effect of CD28 co-stimulation on Rap1 activation. Second, we elucidated the role of Rap1 in T cell activation by expressing the dominant negative Rap1N17 and constitutive active Rap1V12 in DO11.10 hybridoma and Rap1V12 in transgenic mice. Third, we examined the possible involvement of p38 MAPK in Rap1 activation.
Results from our study illustrated CD28 co-stimulation increased Rap1 activation both in EL4 T lymphoma and splenic T cell, supporting a positive role of CD28. The T cell-specific transgenic expression of Rap1V12 did not affect T cell development, including cell number, CD4/CD8 ratio, positive selection and TCR levels. T cell proliferation and IL-2 production were increased in Rap1V12-transgenic mice, suggesting a positive role of Rap1 in T cell activation. In contrast, expression of Rap1V12 and Rap1N17 in DO11.10 T hybridoma did not affect CD3 or antigen peptide induced IL-2 production nor was antigen peptide-mediated T cell-antigen presenting cell conjugation.
In the study of the TCR signals that activate Rap1, we found that pretreatment with p38 MAPK specific inhibitor SB203580 increased TCR-stimulated Rap1 activation in EL4 cell. Pretreatment of splenic T cell with SB203580 resulted in increase Rap1 basal level not TCR-stimulated Rap1 activation. Therefore, the involvement of p38 MAPK in Rap1 activation is cell-type dependent.
In summary, our results clearly support a positive role of Rap1 in the activation of normal T cells. CD28 co-stimulation promoted the Rap1 activation. In addition, p38 MAPK may couple TCR activation to Rap1 activation. However, we also found exceptional results in different types of T cells, suggesting a complicated regulation of Rap1 which may depend on cell type, distribution, and quantity of Rap1. Further studies are required to delineate the exact role of Rap1 in T cell activation and signal coupling.
Subjects
Ｔ細胞活化
Rap1V12轉殖小鼠
T cell activation
Rap1
Rap1V12 transgenic mice
Type
other
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