RasGRP1 transduces low-grade TCR signals which are critical for T cell development, homeostasis, and differentiation
RasGRP1 transduces low-grade TCR signals which are critical for T cell development, homeostasis, and differentiation
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DOI：
10.1016/s1074-7613(02)00451-x
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发表时间：
2002-11-01
期刊：
影响因子：
32.4
通讯作者：
Teh, HS
中科院分区：
文献类型：
--
作者：
Priatel, JJ;Teh, SJ;Teh, HS
两个重要的Ras-鸟苷核苷酸交换因子，Sos和RaSGRP1，控制胸腺细胞中的Ras活化。然而，这两种交换因子对Ras/ERK激活的相对贡献及其对正选择和负选择的影响尚不清楚。我们制备了两系RaSGRP1(-/-) TCR转基因小鼠，以确定在定义的TCR信号条件下，RaSGRP1对T细胞发育的影响。我们的研究结果表明，RasGRP1对于表达弱选择性TCRs的胸腺细胞至关重要，而那些表达强选择性TCRs的胸腺细胞更有效地利用与rasgrpi无关的机制来激活ERK并进行阳性选择。对RaSGRP（-/-）外周T细胞的分析也揭示了RasGRP1在调节T细胞稳态和维持抗原诱导的发育程序中的功能。
Two important Ras-guanyl nucleotide exchange factors, Sos and RaSGRP1, control Ras activation in thymocytes. However, the relative contribution of these two exchange factors to Ras/ERK activation and their resulting impact on positive and negative selection is unclear. We have produced two lines of RaSGRP1(-/-) TCR transgenic mice to determine the effect of RasGRP1 in T cell development under conditions of defined TCR signaling. Our results demonstrate that RasGRP1 is crucial for thymocytes expressing weakly selecting TCRs whereas those that express stronger selecting TCRs are more effective at utilizing RaSGRPi-independent mechanisms for ERK activation and positive selection. Analysis of RaSGRP(-/-) peripheral T cells also revealed hitherto unidentified functions of RasGRP1 in regulating T cell homeostasis and sustaining antigen-induced developmental programming.