Amino acid-dependent NPRL2 interaction with Raptor determines mTOR Complex 1 activation

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We assign a new function to a tumor suppressor NPRL2 that activates the mTOR complex 1 (mTORC1) activity. The positive regulation of mTORC1 activity by NPRL2 is mediated through NPRL2 interaction with Raptor. While NPRL2 interacts with Rag GTPases, RagD in particular, to interfere with mTORC1 activity in amino acid scarcity, NPRL2 interacts with Raptor in amino acid sufficiency to activate mTORC1. A reciprocal relationship exists between NPRL2 binding to Rag GTPases and Raptor. NPRL2 majorly locates in the lysosomal membranes and has a higher binding affinity to the dominant negative mutant heterodimer of RagA(GDP)/RagD(GTP) that inactivates mTORC1. However, the binding affinity of NPRL2 with Raptor is much less pronounced in cells expressing the dominant negative mutant heterodimer of RagA(GDP)/RagD(GTP) than in cells expressing the dominant positive mutant heterodimer, RagA(GTP)/RagD(GDP). The positive effect of NPRL2 on TORC1 pathway was also evidenced in Drosophila animal model. Here, we propose a 'seesaw' model in which the interactive behavior of NPRL2 with Raptor determines mTORC1 activation by amino acid signaling in animal cells. #C# 2015 Elsevier Inc. All rights reserved.
Publisher
ELSEVIER SCIENCE INC
Issue Date
2016-02
Language
English
Article Type
Article
Keywords

HOMOZYGOUS DELETION REGION; HUMAN-CHROMOSOME 3P21.3; TUMOR-SUPPRESSOR GENES; RAG GTPASES; MAMMALIAN TARGET; RAPAMYCIN MTOR; GROWTH; TORC1; DROSOPHILA; PATHWAY

Citation

CELLULAR SIGNALLING, v.28, no.2, pp.32 - 41

ISSN
0898-6568
DOI
10.1016/j.cellsig.2015.11.008
URI
http://hdl.handle.net/10203/207670
Appears in Collection
BS-Journal Papers(저널논문)
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