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首页> 外文期刊>Molecular and Cellular Biology >RasGRF2, a Guanosine Nucleotide Exchange Factor for Ras GTPases, Participates in T-Cell Signaling Responses
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RasGRF2, a Guanosine Nucleotide Exchange Factor for Ras GTPases, Participates in T-Cell Signaling Responses

机译：RasGRF2，Ras GTPases的鸟苷核苷酸交换因子，参与T细胞信号传导反应。

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摘要

The Ras pathway is critical for the development and function of T lymphocytes. The stimulation of this GTPase in T cells occurs primarily through the Vav1- and phospholipase C-γ1-dependent activation of RasGRP1, a diacylglycerol-responsive Ras GDP/GTP exchange factor. Here, we show that a second exchange factor, RasGRF2, also participates in T-cell signaling. RasGRF2 is expressed in T cells, translocates to immune synapses, activates Ras, and stimulates the transcriptional factor NF-AT (nuclear factor of activated T cells) through Ras- and phospholipase C-γ1-dependent routes. T-cell receptor-, Vav1-, and Ca2+-elicited pathways synergize with RasGRF2 for NF-AT stimulation. The analysis of RasGRF2-deficient mice indicates that this protein is required for the induction of bona fide NF-AT targets such as the cytokines tumor necrosis factor alpha and interleukin 2, while it plays minor roles in Ras activation itself. The comparison of lymphocytes from Vav1?/?, Rasgrf2?/?, and Vav1?/?; Rasgrf2?/? mice demonstrates that the RasGRF2 pathway cooperates with the Vav1/RasGRP1 route in the blasting transformation and proliferation of mature T cells. These results identify RasGRF2 as an additional component of the signaling machinery involved in T-cell receptor- and NF-AT-mediated immune responses.
机译：Ras通路对于T淋巴细胞的发育和功能至关重要。 T细胞中这种GTP酶的刺激主要通过RasGRP1（一种二酰基甘油响应的Ras GDP / GTP交换因子）的Vav1-和磷脂酶C-γ1依赖性激活而发生。在这里，我们显示第二个交换因子RasGRF2也参与T细胞信号传导。 RasGRF2在T细胞中表达，易位至免疫突触，激活Ras，并通过Ras和磷脂酶C-γ1依赖性途径刺激转录因子NF-AT（活化T细胞的核因子）。 T细胞受体，Vav1和Ca 2 + 引起的通路与RasGRF2协同刺激NF-AT。对RasGRF2缺陷小鼠的分析表明，该蛋白是诱导真正的NF-AT靶标（例如细胞因子肿瘤坏死因子α和白介素2）所必需的，而它在Ras激活本身中起着很小的作用。 Vav1 ？/？， Rasgrf2 ？/？和 Vav1 的淋巴细胞的比较em> ？/？; Rasgrf2 ？/？小鼠证明RasGRF2途径与Vav1 / RasGRP1途径协同作用，促进了成熟T细胞的爆炸转化和增殖。这些结果确定了RasGRF2是参与T细胞受体和NF-AT介导的免疫反应的信号传导机制的另外一个组成部分。

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