Reactome | RRAGA,B hydrolyzes GTP

RRAGA,B hydrolyzes GTP

Stable Identifier

R-HSA-9640195

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal membrane

ReviewStatus

5/5

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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
7499430	Cloning of a novel family of mammalian GTP-binding proteins (RagA, RagBs, RagB1) with remote similarity to the Ras-related GTPases Brauers, A, Massmann, S, Joost, HG, Becker, W, Schürmann, A	J. Biol. Chem.	1995
26449471	Sestrin2 is a leucine sensor for the mTORC1 pathway Sabatini, DM, Scaria, SM, Saxton, RA, Chantranupong, L, Cantor, JR, Shen, K, Wolfson, RL	Science	2016
25259925	Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling Peng, M, Li, MO, Yin, N	Cell	2014
26586190	Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway Sabatini, DM, Schwartz, TU, Wang, T, Pacold, ME, Saxton, RA, Chantranupong, L, Knockenhauer, KE, Wolfson, RL	Science	2016
30651352	Arg-78 of Nprl2 catalyzes GATOR1-stimulated GTP hydrolysis by the Rag GTPases Sabatini, DM, Gu, X, Valenstein, ML, Shen, K	J. Biol. Chem.	2019
29123071	SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway Sabatini, DM, Scaria, SM, Gu, X, Saxton, RA, Gygi, SP, Liu, GY, Harper, JW, Condon, KJ, Krawczyk, PA, Orozco, JM	Science	2017
27487210	Mechanism of arginine sensing by CASTOR1 upstream of mTORC1 Sabatini, DM, Schwartz, TU, Saxton, RA, Chantranupong, L, Knockenhauer, KE	Nature	2016
28066558	Structural mechanism for the arginine sensing and regulation of CASTOR1 in the mTORC1 signaling pathway Yang, C, Wang, Q, Gai, Z, Deng, W, Wang, L, Wu, G	Cell Discov	2016
25457612	Sestrins inhibit mTORC1 kinase activation through the GATOR complex Budanov, AV, Nourbakhsh, A, Ding, B, Guan, KL, Kim, YC, Akopiants, K, Wang, W, Karin, M, Parmigiani, A	Cell Rep	2014
25263562	The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1 Sabatini, DM, Scaria, SM, Spooner, E, Saxton, RA, Gygi, SP, Bar-Peled, L, Chantranupong, L, Isasa, M, Orozco, JM, Wolfson, RL	Cell Rep	2014
27648300	Structural insight into the arginine-binding specificity of CASTOR1 in amino acid-dependent mTORC1 signaling Ding, J, Wang, R, Zhang, T, Xia, J	Cell Discov	2016
26972053	The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway Sabatini, DM, Wang, T, Scaria, SM, Saxton, RA, Gygi, SP, Gygi, MP, Chantranupong, L, Harper, JW, Wyant, GA, Shen, K	Cell	2016
25819761	Sestrin2 inhibits mTORC1 through modulation of GATOR complexes Lee, JH, Semple, IA, Ro, SH, Cho, US, Guan, KL, Park, H, Park, HW, Kim, M, Wang, W, Karin, M, Kim, JS	Sci Rep	2015
23723238	A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1 Chen, WW, Sabatini, DM, Carter, SL, Spear, ED, Cherniack, AD, Bar-Peled, L, Ottina, KA, Chantranupong, L, Grabiner, BC, Meyerson, M	Science	2013