RRAGD

Summary

Gene Symbol: RRAGD
Description: Ras related GTP binding D
Alias: RAGD, bA11D8.2.1, ras-related GTP-binding protein D, Rag D protein
Species: human
Products:     RRAGD

Top Publications

  1. Sancak Y, Peterson T, Shaul Y, Lindquist R, Thoreen C, Bar Peled L, et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science. 2008;320:1496-501 pubmed publisher
    ..The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb. ..
  2. Han J, Jeong S, Park M, Kim G, Kwon N, Kim H, et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012;149:410-24 pubmed publisher
    ..This work demonstrates that LRS is a key mediator for amino acid signaling to mTORC1. ..
  3. Tsun Z, Bar Peled L, Chantranupong L, Zoncu R, Wang T, Kim C, et al. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol Cell. 2013;52:495-505 pubmed publisher
    ..We identify FLCN and its binding partners, FNIP1/2, as Rag-interacting proteins with GAP activity for RagC/D, but not RagA/B. Thus, we reveal a role for RagC/D in mTORC1 activation and a molecular function for the FLCN tumor suppressor. ..
  4. Sekiguchi T, Hirose E, Nakashima N, Ii M, Nishimoto T. Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag A and Rag B. J Biol Chem. 2001;276:7246-57 pubmed
    ..Both Rag C and Rag D changed their subcellular localization, depending on the nucleotide-bound state of Rag A. In a similar way, the disruption of S. cerevisiae GTR1 resulted in a change in the localization of Gtr2p. ..
  5. Sancak Y, Bar Peled L, Zoncu R, Markhard A, Nada S, Sabatini D. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell. 2010;141:290-303 pubmed publisher
    ..Thus, Rag-Ragulator-mediated translocation of mTORC1 to lysosomal membranes is the key event in amino acid signaling to mTORC1. ..
  6. Sekiguchi T, Furuno N, Ishii T, Hirose E, Sekiguchi F, Wang Y, et al. RagA, an mTORC1 activator, interacts with a hedgehog signaling protein, WDR35/IFT121. Genes Cells. 2019;24:151-161 pubmed publisher
    Small Ras-like GTPases act as molecular switches for various signal transduction pathways. RagA, RagB/RagC and RagD are small Ras-like GTPases that play regulatory roles in mTORC1...
  7. Shen K, Valenstein M, Gu X, Sabatini D. Arg-78 of Nprl2 catalyzes GATOR1-stimulated GTP hydrolysis by the Rag GTPases. J Biol Chem. 2019;294:2970-2975 pubmed publisher
    ..GTPase heterodimer has a unique architecture that consists of two GTPase subunits, RagA or RagB bound to RagC or RagD. Their nucleotide-loading states are strictly controlled by several lysosomal or cytosolic protein complexes that ..
  8. Lima R, Sousa D, Gomes A, Mendes N, Matthiesen R, Pedro M, et al. The Antitumor Activity of a Lead Thioxanthone is Associated with Alterations in Cholesterol Localization. Molecules. 2018;23: pubmed publisher
    ..Our results showed that TXA1.HCl affected steroid biosynthesis, increased RagD expression, and caused abnormal cellular cholesterol localization. In addition, TXA1...
  9. Mu Y, Zheng D, Wang C, Yu W, Zhang X. RagD regulates amino acid mediated-casein synthesis and cell proliferation via mTOR signalling in cow mammary epithelial cells. J Dairy Res. 2018;85:204-211 pubmed publisher
    This research paper addresses the hypothesis that RagD is a key signalling factor that regulates amino acid (AA) mediated-casein synthesis and cell proliferation in cow mammary epithelial cells (CMECs)...

More Information

Publications29

  1. Shen K, Sabatini D. Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms. Proc Natl Acad Sci U S A. 2018;115:9545-9550 pubmed publisher
    ..that converge on the Rag GTPases, which form heterodimers consisting of RagA or RagB tightly bound to RagC or RagD and control the subcellular localization of mTORC1...
  2. Lee M, Kim J, Yoon I, Lee C, Fallahi Sichani M, Kang J, et al. Coordination of the leucine-sensing Rag GTPase cycle by leucyl-tRNA synthetase in the mTORC1 signaling pathway. Proc Natl Acad Sci U S A. 2018;115:E5279-E5288 pubmed publisher
    ..Rag GTPase cycle during leucine signaling and that LRS serves as an initiating "ON" switch via GTP hydrolysis of RagD that drives the entire Rag GTPase cycle, whereas Sestrin2 functions as an "OFF" switch by controlling GTP ..
  3. Chantranupong L, Wolfson R, Orozco J, Saxton R, Scaria S, Bar Peled L, et al. The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep. 2014;9:1-8 pubmed publisher
    ..A key input is amino acids, which act through the heterodimeric Rag GTPases (RagA or RagB bound to RagC or RagD) in order to promote the translocation of mTORC1 to the lysosomal surface, its site of activation...
  4. Parmigiani A, Nourbakhsh A, Ding B, Wang W, Kim Y, Akopiants K, et al. Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep. 2014;9:1281-91 pubmed
    ..mTORC1 is activated by Rag GTPases, working as RagA:RagB and RagC:RagD heterodimers...
  5. Péli Gulli M, Sardu A, Panchaud N, Raucci S, De Virgilio C. Amino Acids Stimulate TORC1 through Lst4-Lst7, a GTPase-Activating Protein Complex for the Rag Family GTPase Gtr2. Cell Rep. 2015;13:1-7 pubmed publisher
    Rag GTPases assemble into heterodimeric complexes consisting of RagA or RagB and RagC or RagD in higher eukaryotes, or Gtr1 and Gtr2 in yeast, to relay amino acid signals toward the growth-regulating target of rapamycin complex 1 (TORC1)...
  6. Kwak S, Kang K, Kim S, Lee S, Lee J, Kim J, et al. Amino acid-dependent NPRL2 interaction with Raptor determines mTOR Complex 1 activation. Cell Signal. 2016;28:32-41 pubmed publisher
    ..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 ..
  7. He L, Hamm J, Reddy A, Sams D, Peliciari Garcia R, McGinnis G, et al. Biotinylation: a novel posttranslational modification linking cell autonomous circadian clocks with metabolism. Am J Physiol Heart Circ Physiol. 2016;310:H1520-32 pubmed publisher
    ..Furthermore, data suggest that the RRAGD/mTOR/4E-BP1 signaling axis is chronically activated in CBK and CCM hearts...
  8. Kim C, Jung J, Tung T, Park S. ?-Turn mimetic-based stabilizers of protein-protein interactions for the study of the non-canonical roles of leucyl-tRNA synthetase. Chem Sci. 2016;7:2753-2761 pubmed publisher
    ..Each library member was subjected to ELISA-based modulator screening for the LRS-RagD interaction, which plays a pivotal role in the nutrient-dependent mTORC1 signalling pathway...
  9. Kim J, Jung J, Koo J, Cho W, Lee W, Kim C, et al. Diversity-oriented synthetic strategy for developing a chemical modulator of protein-protein interaction. Nat Commun. 2016;7:13196 pubmed publisher
    ..To validate the utility of this DOS library, we identify a new small-molecule inhibitor of leucyl-tRNA synthetase-RagD protein-protein interaction, which regulates the amino acid-dependent activation of mechanistic target of rapamycin ..
  10. Rebsamen M, Pochini L, Stasyk T, de Araújo M, Galluccio M, Kandasamy R, et al. SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature. 2015;519:477-81 pubmed publisher
    ..Thus SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR. ..
  11. Di Malta C, Siciliano D, Calcagnì A, Monfregola J, Punzi S, Pastore N, et al. Transcriptional activation of RagD GTPase controls mTORC1 and promotes cancer growth. Science. 2017;356:1188-1192 pubmed publisher
    ..biogenesis and autophagy-control mTORC1 lysosomal recruitment and activity by directly regulating the expression of RagD. In mice, this mechanism mediated adaptation to food availability after starvation and physical exercise and played ..
  12. Choi H, Son J, Kang J, Kwon J, Kim J, Jung M, et al. Leucine-induced localization of Leucyl-tRNA synthetase in lysosome membrane. Biochem Biophys Res Commun. 2017;493:1129-1135 pubmed publisher
    ..The translocation was inhibited by treatment with compound BC-LI-0186, disrupting the interaction between RagD and LRS. Immuno-TEM revealed a clear decrease in LRS translocation to the lysosome on addition of the inhibitor...
  13. Oshiro N, Rapley J, Avruch J. Amino acids activate mammalian target of rapamycin (mTOR) complex 1 without changing Rag GTPase guanyl nucleotide charging. J Biol Chem. 2014;289:2658-74 pubmed publisher
    ..Such a mutation in RagA or RagB inhibits, whereas in RagC or RagD it enhances, Rag heterodimer binding to mTORC1...
  14. Chauhan S, Kumar S, Jain A, Ponpuak M, Mudd M, Kimura T, et al. TRIMs and Galectins Globally Cooperate and TRIM16 and Galectin-3 Co-direct Autophagy in Endomembrane Damage Homeostasis. Dev Cell. 2016;39:13-27 pubmed publisher
    ..The cooperation between TRIM16 and Galectin-3 in targeting and activation of selective autophagy protects cells from lysosomal damage and Mycobacterium tuberculosis invasion. ..
  15. Peng M, Yin N, Li M. Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling. Cell. 2014;159:122-133 pubmed publisher
    ..These findings reveal a nonredundant mechanism by which the Sestrin family of GDIs regulates the nutrient-sensing Rag GTPases to control mTORC1 signaling. ..
  16. Demetriades C, Doumpas N, Teleman A. Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2. Cell. 2014;156:786-99 pubmed publisher
    ..These data suggest that regulation of TSC2 subcellular localization may be a general mechanism to control its activity and place TSC2 in the amino-acid-sensing pathway to TORC1...
  17. Kim Y, Stone M, Hwang T, Kim Y, Dunlevy J, Griffin T, et al. SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signaling. Mol Cell. 2012;46:833-46 pubmed publisher
    ..These results demonstrate that SH3BP4 is a negative regulator of the Rag GTPase complex and amino acid-dependent mTORC1 signaling. ..
  18. de Wit N, Rijntjes J, Diepstra J, van Kuppevelt T, Weidle U, Ruiter D, et al. Analysis of differential gene expression in human melanocytic tumour lesions by custom made oligonucleotide arrays. Br J Cancer. 2005;92:2249-61 pubmed
    ..For at least nine of these genes, namely THBD, FABP7, H2AFJ, RRAGD, MYADM, HR, CKS2, NCK2 and GDF15, the differential expression found by array analyses could be verified by ..
  19. Sekiguchi T, Todaka Y, Wang Y, Hirose E, Nakashima N, Nishimoto T. A novel human nucleolar protein, Nop132, binds to the G proteins, RRAG A/C/D. J Biol Chem. 2004;279:8343-50 pubmed
    ..Nop132 also interacts with human Nip7 and is colocalized with RRAG A, RRAG C, and Nip7. RNA interference knockdown of Nop132 inhibited cell growth of HeLa cells. ..
  20. Kim J, Lee C, Lee M, Wang H, Kim K, Park S, et al. Control of leucine-dependent mTORC1 pathway through chemical intervention of leucyl-tRNA synthetase and RagD interaction. Nat Commun. 2017;8:732 pubmed publisher
    ..For further analysis, we selected one compound, BC-LI-0186, which binds to the RagD interacting site of LRS, thereby inhibiting lysosomal localization of LRS and mTORC1 activity...