A role for p120 RasGAP in thymocyte positive selection and survival of naive T cells.
A role for p120 RasGAP in thymocyte positive selection and survival of naive T cells.
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DOI：
10.4049/jimmunol.1100178
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
King PD
中科院分区：
文献类型：
--
作者：
Lapinski PE;Qiao Y;Chang CH;King PD
Ras小gtp结合蛋白的激活是正常T细胞发育和功能所必需的。然而，在众多Ras GTPase激活蛋白（RasGAPs）中，哪一种使T细胞中的Ras失活尚不清楚。我们使用T细胞特异性RASA1缺陷小鼠模型来研究p120 RasGAP蛋白（RASA1）在T细胞中的作用。在rasa1缺陷小鼠中，CD4+CD8+双阳性（DP）胸腺细胞的死亡增加。尽管如此，在MHC ii类限制性TCR转基因背景下，有证据表明胸腺细胞的阳性选择增加与Ras-MAPK途径的增强激活相关。在外周，RASA1被发现作为Ras-MAPK激活和由完全激动肽诱导的T细胞功能反应的调节因子是必不可少的。然而，在rasa1缺陷小鼠中，naïve T细胞的数量显著减少。在RASA1缺失的情况下，naïve T细胞的损失可能部分归因于对IL-7促生存细胞因子的反应性受损。这些发现揭示了RASA1作为胸腺DP存活和阳性选择以及外周血naïve T细胞存活的调节因子的重要作用。
Activation of the Ras small GTP-binding protein is necessary for normal T cell development and function. However, which of a number of Ras GTPase activating proteins (RasGAPs) inactivate Ras in T cells is unknown. We used a T cell-specific RASA1-deficient mouse model to investigate the role of the p120 RasGAP protein (RASA1) in T cells. Death of CD4+CD8+ double-positive (DP) thymocytes was increased in RASA1-deficient mice. Despite this, on an MHC class II-restricted TCR transgenic background, evidence was obtained for increased positive selection of thymocytes associated with augmented activation of the Ras-MAPK pathway. In the periphery, RASA1 was found to be dispensable as a regulator of Ras-MAPK activation and T cell functional responses induced by full agonist peptides. However, numbers of naïve T cells were substantially reduced in RASA1-deficient mice. Loss of naïve T cells in the absence of RASA1 could be attributed in part to impaired responsiveness to the IL-7 pro-survival cytokine. These findings reveal an important role for RASA1 as a regulator of DP survival and positive selection in the thymus as well as naïve T cell survival in the periphery.
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DOI：
10.4049/jimmunol.181.11.7778
发表时间：
2008-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lauritsen JP;Kurella S;Lee SY;Lefebvre JM;Rhodes M;Alberola-Ila J;Wiest DL
通讯作者：
Wiest DL
影响因子：
32.4
作者：
Ernst, B;Lee, DS;Surh, CD
通讯作者：
Surh, CD
影响因子：
4.8
作者：
Cai, Beibei;Chang, Sandra H.;Xia, Zhengui
通讯作者：
Xia, Zhengui
影响因子：
32.4
作者：
Priatel, JJ;Teh, SJ;Teh, HS
通讯作者：
Teh, HS
影响因子：
64.8
作者：
HENKEMEYER, M;ROSSI, DJ;PAWSON, T
通讯作者：
PAWSON, T