Regulation of mTORC1 by amino acids

被引:600
|
作者
Bar-Peled, Liron [1 ]
Sabatini, David M. [2 ,3 ,4 ,5 ,6 ]
机构
[1] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
[2] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[3] MIT, Dept Biol, Cambridge, MA 02142 USA
[4] Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
[5] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA
[6] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA
基金
美国国家卫生研究院;
关键词
amino acid sensing; GATOR complex; Ragulator; Rag GTPases; folliculin; TUMOR-SUPPRESSOR COMPLEX; TUBEROUS SCLEROSIS GENE; TRANSFER-RNA SYNTHETASE; GTP-BINDING PROTEINS; P70; S6; KINASE; RAG GTPASES; CELL-GROWTH; CRYSTAL-STRUCTURE; EGO COMPLEX; 3-KINASE/AKT PATHWAY;
D O I
10.1016/j.tcb.2014.03.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The mechanistic target of rapamycin complex I (mTORC1) is a central regulator of cellular and organismal growth, and hyperactivation of this pathway is implicated in the pathogenesis of many human diseases including cancer and diabetes. mTORC1 promotes growth in response to the availability of nutrients, such as amino acids, which drive mTORC1 to the lysosomal surface, its site of activation. How amino acid levels are communicated to mTORC1 is only recently coming to light by the discovery of a lysosome-based signaling system composed of Rags (Ras-related GTPases) and Ragulator v-ATPase, GATOR (GAP activity towards Rags), and folliculin (FLCN) complexes. Increased understanding of this pathway will not only provide insight into growth control but also into the human pathologies triggered by its deregulation.
引用
收藏
页码:400 / 406
页数:7
相关论文
共 50 条
  • [1] Differential Regulation of mTORC1 by Amino Acids
    Jewell, Jenna L.
    Guan, Kun-Liang
    FASEB JOURNAL, 2016, 30
  • [2] Lysosomal Regulation of mTORC1 by Amino Acids in Mammalian Cells
    Yao, Yao
    Jones, Edith
    Inoki, Ken
    BIOMOLECULES, 2017, 7 (03):
  • [3] Mechanisms Involved in the Coordinate Regulation of mTORC1 by Insulin and Amino Acids
    Dennis, Michael D.
    Baum, Jamie I.
    Kimball, Scot R.
    Jefferson, Leonard S.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (10) : 8287 - 8296
  • [4] Spatial regulation of the mTORC1 system in amino acids sensing pathway
    Suzuki, Tsukasa
    Inoki, Ken
    ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2011, 43 (09) : 671 - 679
  • [5] The regulation of mTORC1 signaling by amino acids in skeletal muscle of neonatal pigs
    Suryawan, Agus
    Nguyen, Hanh V.
    Davis, Teresa A.
    AMINO ACIDS, 2013, 45 (03) : 584 - 584
  • [6] Amino acid sensing and regulation of mTORC1
    Yan, Lijun
    Lamb, Richard F.
    SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2012, 23 (06) : 621 - 625
  • [7] A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids
    Gollwitzer, Peter
    Grutzmacher, Nina
    Wilhelm, Sabine
    Kummel, Daniel
    Demetriades, Constantinos
    NATURE CELL BIOLOGY, 2022, 25 (2) : 366 - 366
  • [8] A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids
    Peter Gollwitzer
    Nina Grützmacher
    Sabine Wilhelm
    Daniel Kümmel
    Constantinos Demetriades
    Nature Cell Biology, 2022, 24 : 1394 - 1406
  • [9] A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids
    Gollwitzer, Peter
    Gruetzmacher, Nina
    Wilhelm, Sabine
    Kuemmel, Daniel
    Demetriades, Constantinos
    NATURE CELL BIOLOGY, 2022, 24 (09) : 1394 - +
  • [10] Dynamics of mTORC1 activation in response to amino acids
    Manifava, Maria
    Smith, Matthew
    Rotondo, Sergio
    Walker, Simon
    Niewczas, Izabella
    Zoncu, Roberto
    Clark, Jonathan
    Ktistakis, Nicholas T.
    ELIFE, 2016, 5