硒蛋白与GATOR2相互作用，以负向调节mTORC1上游的氨基酸感应通路。
The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1.
作者信息
Chantranupong Lynne, Wolfson Rachel L, Orozco Jose M, Saxton Robert A, Scaria Sonia M, Bar-Peled Liron, Spooner Eric, Isasa Marta, Gygi Steven P, Sabatini David M
机构信息
Department of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge MA 02142, USA.
Department of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Cell Rep. 2014 Oct 9;9(1):1-8. doi: 10.1016/j.celrep.2014.09.014. Epub 2014 Sep 25.
The mechanistic target of rapamycin complex 1 (mTORC1) kinase is a major regulator of cell growth that responds to numerous environmental cues. A key input is amino acids, which act through the heterodimeric Rag GTPases (RagA or RagB bound to RagC or RagD) in order to promote the translocation of mTORC1 to the lysosomal surface, its site of activation. GATOR2 is a complex of unknown function that positively regulates mTORC1 signaling by acting upstream of or in parallel to GATOR1, which is a GTPase-activating protein (GAP) for RagA or RagB and an inhibitor of the amino-acid-sensing pathway. Here, we find that the Sestrins, a family of poorly understood growth regulators (Sestrin1-Sestrin3), interact with GATOR2 in an amino-acid-sensitive fashion. Sestrin2-mediated inhibition of mTORC1 signaling requires GATOR1 and the Rag GTPases, and the Sestrins regulate the localization of mTORC1 in response to amino acids. Thus, we identify the Sestrins as GATOR2-interacting proteins that regulate the amino-acid-sensing branch of the mTORC1 pathway.
雷帕霉素靶蛋白复合物1（mTORC1）激酶是细胞生长的主要调节因子，可对多种环境信号作出反应。一个关键的输入信号是氨基酸，其通过异源二聚体Rag GTP酶（与RagC或RagD结合的RagA或RagB）发挥作用，以促进mTORC1转运至溶酶体表面，即其激活位点。GATOR2是一个功能未知的复合物，通过在GATOR1的上游或与其平行发挥作用来正向调节mTORC1信号传导，GATOR1是RagA或RagB的GTP酶激活蛋白（GAP），也是氨基酸感应途径的抑制剂。在此，我们发现Sesrins，一类了解较少的生长调节因子家族（Sestrin1 - Sestrin3），以氨基酸敏感的方式与GATOR2相互作用。Sestrin2介导的对mTORC1信号传导的抑制作用需要GATOR1和Rag GTP酶，并且Sesrins可响应氨基酸调节mTORC1的定位。因此，我们确定Sesrins是与GATOR2相互作用的蛋白，可调节mTORC1途径的氨基酸感应分支。
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