RRAGA,B hydrolyzes GTP

Stable Identifier
R-HSA-9640195
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The GTPase activity of RRAGA,B hydrolyzes GTP to GDP (Bar-Peled et al. 2013). RRAGA and RRAGB lack detectable GTPase activity in the absence of a GTPase activating protein (Schurmann et al. 1995). The NPRL2 subunit of the GATOR1 complex acts as a GTPase activator of RRAGA,B and thereby controls the guanyl nucleotide bound to RRAGA,B (Bar-Peled et al. 2013, Shen et al. 2019). GATOR2 antagonizes GATOR1 (Bar-Peled et al. 2013). During amino acid deficiency, Sestrins (SESN1 and SESN2) (Chantranupong et al. 2014, Parmigiani et al. 2014, Peng et al. 2014, Kim et al. 2015, Wolfson et al. 2016, Saxton et al. 2016) and CASTOR1 (Chantranupong et al. 2016, Saxton et al. 2016, Gai et al. 2016, Xia et al. 2016) bound to GATOR2 prevent GATOR2 from antagonizing GATOR1 (Bar-Peled et al. 2013). BMT2 (SAMTOR) bound to GATOR1 enhances inhibition of mTORC1 activation by GATOR1 (Gu et al. 2017).

Literature References
PubMed ID Title Journal Year
25819761 Sestrin2 inhibits mTORC1 through modulation of GATOR complexes

Kim, JS, Ro, SH, Kim, M, Park, HW, Semple, IA, Park, H, Cho, US, Wang, W, Guan, KL, Karin, M, Lee, JH

Sci Rep 2015
23723238 A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1

Bar-Peled, L, Chantranupong, L, Cherniack, AD, Chen, WW, Ottina, KA, Grabiner, BC, Spear, ED, Carter, SL, Meyerson, M, Sabatini, DM

Science 2013
26972053 The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway

Chantranupong, L, Scaria, SM, Saxton, RA, Gygi, MP, Shen, K, Wyant, GA, Wang, T, Harper, JW, Gygi, SP, Sabatini, DM

Cell 2016
27648300 Structural insight into the arginine-binding specificity of CASTOR1 in amino acid-dependent mTORC1 signaling

Xia, J, Wang, R, Zhang, T, Ding, J

Cell Discov 2016
25263562 The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1

Chantranupong, L, Wolfson, RL, Orozco, JM, Saxton, RA, Scaria, SM, Bar-Peled, L, Spooner, E, Isasa, M, Gygi, SP, Sabatini, DM

Cell Rep 2014
25457612 Sestrins inhibit mTORC1 kinase activation through the GATOR complex

Parmigiani, A, Nourbakhsh, A, Ding, B, Wang, W, Kim, YC, Akopiants, K, Guan, KL, Karin, M, Budanov, AV

Cell Rep 2014
28066558 Structural mechanism for the arginine sensing and regulation of CASTOR1 in the mTORC1 signaling pathway

Gai, Z, Wang, Q, Yang, C, Wang, L, Deng, W, Wu, G

Cell Discov 2016
27487210 Mechanism of arginine sensing by CASTOR1 upstream of mTORC1

Saxton, RA, Chantranupong, L, Knockenhauer, KE, Schwartz, TU, Sabatini, DM

Nature 2016
29123071 SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway

Gu, X, Orozco, JM, Saxton, RA, Condon, KJ, Liu, GY, Krawczyk, PA, Scaria, SM, Harper, JW, Gygi, SP, Sabatini, DM

Science 2017
30651352 Arg-78 of Nprl2 catalyzes GATOR1-stimulated GTP hydrolysis by the Rag GTPases

Shen, K, Valenstein, ML, Gu, X, Sabatini, DM

J. Biol. Chem. 2019
26586190 Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway

Saxton, RA, Knockenhauer, KE, Wolfson, RL, Chantranupong, L, Pacold, ME, Wang, T, Schwartz, TU, Sabatini, DM

Science 2016
25259925 Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling

Peng, M, Yin, N, Li, MO

Cell 2014
26449471 Sestrin2 is a leucine sensor for the mTORC1 pathway

Wolfson, RL, Chantranupong, L, Saxton, RA, Shen, K, Scaria, SM, Cantor, JR, Sabatini, DM

Science 2016
7499430 Cloning of a novel family of mammalian GTP-binding proteins (RagA, RagBs, RagB1) with remote similarity to the Ras-related GTPases

Schürmann, A, Brauers, A, Massmann, S, Becker, W, Joost, HG

J. Biol. Chem. 1995
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
GTPase activity of v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP:mTORC1:RHEB:GTP [lysosomal membrane]
Physical Entity
Activity
This event is regulated
Orthologous Events
Authored
Reviewed
Created
Cite Us!