Vav1 的核苷酸交换活性在 T 细胞发育和激活中的功能。
Function of the nucleotide exchange activity of vav1 in T cell development and activation.
机构信息
1Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, UK.
出版信息
Sci Signal. 2009 Dec 15;2(101):ra83. doi: 10.1126/scisignal.2000420.
Abstract
The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal-regulated kinase and protein kinase D1, and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions.
摘要
鸟苷酸交换因子（GEF）Vav1 对于传递 T 细胞抗原受体（TCR）信号至关重要，因此在 T 细胞的发育和激活中发挥着关键作用。人们推测 Vav1 的 GEF 活性对其功能很重要；然而，这一点尚未得到直接证明。在这里，我们生成了表达酶失活但正常折叠的 Vav1 蛋白的小鼠。对这些小鼠的分析表明，Vav1 的 GEF 活性对于胸腺细胞的选择以及 T 细胞的最佳激活是必要的，包括 Rac1、Akt 和整合素的信号转导。相比之下，Vav1 的 GEF 活性对于 TCR 诱导的钙流、细胞外信号调节激酶和蛋白激酶 D1 的激活以及细胞极化并不必需。因此，在 T 细胞中，Vav1 的 GEF 活性对于其某些而非所有功能是必需的。
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