Nitrogen Source Activates TOR (Target of Rapamycin) Complex 1 via Glutamine and Independently of Gtr/Rag Proteins
Nitrogen Source Activates TOR (Target of Rapamycin) Complex 1 via Glutamine and Independently of Gtr/Rag Proteins
复制标题
DOI：
10.1074/jbc.m114.574335
复制
发表时间：
2014-09-05
影响因子：
4.8
通讯作者：
Hall, Michael N.
中科院分区：
文献类型：
--
作者：
Stracka, Daniele;Jozefczuk, Szymon;Hall, Michael N.
进化保守的TOR复合物1（TORC 1）激活细胞生长以响应营养。在酵母中，TORC 1通过一种知之甚少的机制对氮源做出反应。亮氨酸，也许还有其他氨基酸，通过小GTP酶Gtr 1和Gtr 2（哺乳动物Rag GTP酶的直系同源物）激活TORC 1。在这里，我们研究了氮源对TORC 1的激活，以及这可能与GTR/Rag对TORC 1的激活有关。氮源的质量，如其促进生长和谷氨酰胺积累的能力所定义的，与其激活TORC 1的能力直接相关，如通过Sch 9磷酸化所测量的。优选的氮源刺激快速、持续的Sch 9磷酸化和谷氨酰胺积累。谷氨酰胺合成的抑制降低TORC 1活性和生长。贫氮源刺激快速但短暂的Sch 9磷酸化。Gtr 1缺陷阻止TORC 1的瞬时刺激，但不影响TORC 1响应良好氮源的持续活性。这些发现表明，氮源必须转化为谷氨酰胺，在酵母中的首选氮源，以维持TORC 1活性。此外，持续的TORC 1活性不依赖于Gtr/Rag。因此，氮源和Gtr/Rag通过不同的机制激活TORC 1。
The evolutionary conserved TOR complex 1 (TORC1) activates cell growth in response to nutrients. In yeast, TORC1 responds to the nitrogen source via a poorly understood mechanism. Leucine, and perhaps other amino acids, activates TORC1 via the small GTPases Gtr1 and Gtr2, orthologs of the mammalian Rag GTPases. Here we investigate the activation of TORC1 by the nitrogen source and how this might be related to TORC1 activation by Gtr/Rag. The quality of the nitrogen source, as defined by its ability to promote growth and glutamine accumulation, directly correlates with its ability to activate TORC1 as measured by Sch9 phosphorylation. Preferred nitrogen sources stimulate rapid, sustained Sch9 phosphorylation and glutamine accumulation. Inhibition of glutamine synthesis reduces TORC1 activity and growth. Poor nitrogen sources stimulate rapid but transient Sch9 phosphorylation. A Gtr1 deficiency prevents the transient stimulation of TORC1 but does not affect the sustained TORC1 activity in response to good nitrogen sources. These findings suggest that the nitrogen source must be converted to glutamine, the preferred nitrogen source in yeast, to sustain TORC1 activity. Furthermore, sustained TORC1 activity is independent of Gtr/Rag. Thus, the nitrogen source and Gtr/Rag activate TORC1 via different mechanisms.