Regulation of TORC1 by Rag GTPases in nutrient response.

Regulation of TORC1 by Rag GTPases in nutrient response.
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DOI:
10.1038/ncb1753
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发表时间:
2008-08
影响因子:
21.3
通讯作者:
Guan, Kun-Liang
Guan, Kun-Liang
中科院分区:
生物学1区
文献类型:
--
作者:
Kim, Eunjung;Goraksha-Hicks, Pankuri;Li, Li;Neufeld, Thomas P.;Guan, Kun-Liang

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TORC1(雷帕霉素复合物1的靶标)在调节细胞生长和细胞大小方面具有关键作用。已知包括氨基酸在内的多种信号可激活TORC 1。在这里,我们报告的Rag GTP酶作为新的激活剂的TORC1在响应氨基酸信号的识别。Rag基因表达的敲低抑制了果蝇S2细胞中氨基酸对TORC 1的刺激作用。在哺乳动物细胞中表达组成型活性(GTP结合)Rag增强TORC1在氨基酸的情况下,而显性负Rag的表达阻断氨基酸对TORC1的刺激作用。果蝇遗传学研究还表明,Rag GTP酶调节细胞生长,自噬和饥饿下的动物生存能力。总之,我们的研究建立了一个新的功能Rag GTP酶在TORC 1激活响应氨基酸信号。
TORC1 (Target of rapamycin complex 1) has a critical role in the regulation of cell growth and cell size. A wide range of signals, including amino acids, is known to activate TORC1. Here, we report the identification of Rag GTPases as novel activators of TORC1 in response to amino acid signals. Knockdown of Rag gene expression suppressed the stimulatory effect of amino acids on TORC1 in Drosophila S2 cells. Expression of constitutively active (GTP-bound) Rag in mammalian cells enhances TORC1 in the absence of amino acids while expression of dominant negative Rag blocks the stimulatory effects of amino acids on TORC1. Drosophila genetic studies also show that the Rag GTPases regulate cell growth, autophagy, and animal viability under starvation. Together, our studies establish a novel function of Rag GTPases in TORC1 activation in response to amino acid signals.
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发表时间: 2005-07-01
期刊: MOLECULAR CELL
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