v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP binds mTORC1

Stable Identifier
R-HSA-9645608
Type
Reaction [binding]
Species
Homo sapiens
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The heterodimer comprising RRAGA,B:GTP and RRAGC,D:GDP (RagA:GTP or RagB:GTP complexed with RagC:GDP or RagD:GDP) forms the active conformation of the Rag complex that recruits the mTORC1 complex from the cytosol to the lysosomal membrane (Kim et al. 2008, Sancak et al. 2008, Sancak et al. 2010) where RHEB activates the protein kinase activity of mTORC1. Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 (Zoncu et al. 2011). The active state of the RRAGA,B:RRAGC,D heterodimer is less stably associated with the Ragulator complex and appears to cycle with mTORC1 between the lysosomal membrane and the cytosol (Lawrence et al. 2018). The cycling may provide a mechanism for attenuating mTORC1 signaling.

Literature References
PubMed ID Title Journal Year
22053050 mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase

Zoncu, R, Bar-Peled, L, Efeyan, A, Wang, S, Sancak, Y, Sabatini, DM

Science 2011
20381137 Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids

Sancak, Y, Bar-Peled, L, Zoncu, R, Markhard, AL, Nada, S, Sabatini, DM

Cell 2010
18497260 The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1

Sancak, Y, Peterson, TR, Shaul, YD, Lindquist, RA, Thoreen, CC, Bar-Peled, L, Sabatini, DM

Science 2008
18604198 Regulation of TORC1 by Rag GTPases in nutrient response

Kim, E, Goraksha-Hicks, P, Li, L, Neufeld, TP, Guan, KL

Nat. Cell Biol. 2008
30061680 A nutrient-induced affinity switch controls mTORC1 activation by its Rag GTPase-Ragulator lysosomal scaffold

Lawrence, RE, Cho, KF, Rappold, R, Thrun, A, Tofaute, M, Kim, DJ, Moldavski, O, Hurley, JH, Zoncu, R

Nat. Cell Biol. 2018
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