RRAGA

Summary

Gene Symbol: RRAGA
Description: Ras related GTP binding A
Alias: FIP-1, FIP1, RAGA, ras-related GTP-binding protein A, adenovirus E3 14.7 kDa-interacting protein 1, adenovirus E3-14.7K interacting protein 1, rag A
Species: human
Products:     RRAGA

Top Publications

  1. Sun C, Hu Y, Chu Z, Guo T, He J. Successful treatment of myeloid neoplasms associated with PDGFRA rearrangement with imatinib mesylate. Int J Hematol. 2009;89:66-70 pubmed publisher
    ..Despite patients with FIP1-like-1-platelet-derived growth factor alpha (FIP1L1-PDGFRA) associated HES (myeloid neoplasms associated with ..
  2. Rozenblatt Rosen O, Nagaike T, FRANCIS J, Kaneko S, Glatt K, Hughes C, et al. The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3' mRNA processing factors. Proc Natl Acad Sci U S A. 2009;106:755-60 pubmed publisher
    ..Our results suggest that Cdc73 facilitates association of 3' mRNA processing factors with actively-transcribed chromatin and support the importance of links between tumor suppression and mRNA maturation. ..
  3. Ogbogu P, Bochner B, Butterfield J, Gleich G, Huss Marp J, Kahn J, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009;124:1319-25.e3 pubmed publisher
    ..Eighteen of 161 patients (11%) tested were Fip1-like 1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) mutation-positive, and 29 of 168 patients ..
  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
    b>Rag A/Gtr1p are G proteins and are known to be involved in the RCC1-Ran pathway. We employed the two-hybrid method using Rag A as the bait to identify proteins binding to Rag A, and we isolated two novel human G proteins, Rag C and Rag D...
  5. 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. ..
  6. Bar Peled L, Schweitzer L, Zoncu R, Sabatini D. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell. 2012;150:1196-208 pubmed publisher
    ..The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form a signaling ..
  7. 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. ..
  8. Gong R, Li L, Liu Y, Wang P, Yang H, Wang L, et al. Crystal structure of the Gtr1p-Gtr2p complex reveals new insights into the amino acid-induced TORC1 activation. Genes Dev. 2011;25:1668-73 pubmed publisher
    ..The heterodimeric GTPases reveal a pseudo-twofold symmetric organization. Structure-guided functional analyses of RagA-RagC, the human homologs of Gtr1p-Gtr2p, show that both G domains (N-terminal GTPase domains) and dimerization are ..
  9. Bar Peled L, Chantranupong L, Cherniack A, Chen W, Ottina K, Grabiner B, et al. A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science. 2013;340:1100-6 pubmed publisher
    ..GATOR1 has GTPase-activating protein (GAP) activity for RagA and RagB, and its components are mutated in human cancer...

More Information

Publications101 found, 100 shown here

  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. Li L, Baxter S, Zhao P, Gu N, Zhan X. Differential interactions of missing in metastasis and insulin receptor tyrosine kinase substrate with RAB proteins in the endocytosis of CXCR4. J Biol Chem. 2019;294:6494-6505 pubmed publisher
    ..Hence, to the best of our knowledge, our results provide first evidence that the SH3 domain is critical in the regulation of specific endocytic pathways by I-BAR domain proteins. ..
  3. Pal R, Palmieri M, Chaudhury A, Klisch T, di Ronza A, Neilson J, et al. Src regulates amino acid-mediated mTORC1 activation by disrupting GATOR1-Rag GTPase interaction. Nat Commun. 2018;9:4351 pubmed publisher
    ..Rag GTPase-GATOR1 interactions inhibit mTORC1 in the absence of amino acids, and GATOR1 release and activation of RagA/B promotes mTORC1 activity in the presence of amino acids...
  4. Meireles A, Shen K, Zoupi L, Iyer H, Bouchard E, Williams A, et al. The Lysosomal Transcription Factor TFEB Represses Myelination Downstream of the Rag-Ragulator Complex. Dev Cell. 2018;47:319-330.e5 pubmed publisher
    ..Here, we show that the lysosomal G protein RagA is essential for CNS myelination. In rraga-/- mutant oligodendrocytes, target genes of the lysosomal transcription factor Tfeb are upregulated, ..
  5. Sakai R, Fukuda R, Unida S, Aki M, Ono Y, Endo A, et al. The integral function of the endocytic recycling compartment is regulated by RFFL-mediated ubiquitylation of Rab11 effectors. J Cell Sci. 2019;132: pubmed publisher
    ..these Rab11 effectors in vitro, but RFFL knockout (KO) only reduced the ubiquitylation of Rab11-FIP1. RFFL KO had a minimal effect on the ubiquitylation of EHD1, MICALL1, and Rab11-FIP2, and failed to delay ..
  6. SÁnchez S, Goldstein L, Dronen N. Diphyllobothrium stemmacephalum Cobbold, 1858 (Diphyllobothriidea) from common bottlenose dolphin, Tursiops truncatus (Montagu) from the Texas Gulf coast, USA. Zootaxa. 2018;4379:448-450 pubmed publisher
    ..1997); long-finned pilot whale, Globicephala melas [Traill], North Atlantic off Faroe Island (Balbuena Raga 1993); Atlantic white-sided dolphin, Lagenorhynchus acutus [Gray], off Massachusetts (Olson Caira 1999).
  7. Zhou Y, Wang C, Xiao Q, Guo L. Crystal structures of arginine sensor CASTOR1 in arginine-bound and ligand free states. Biochem Biophys Res Commun. 2019;508:387-391 pubmed publisher
    ..Arginine Sensor of mTORC1) from GATOR2, a positive regulator of mTORC1 which interacts with GATOR1, the GAP for RagA/B...
  8. Cinti A, Le Sage V, Milev M, Valiente Echeverría F, Crossie C, Miron M, et al. HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases. Sci Rep. 2017;7:5515 pubmed publisher
    ..We then show that the small Rag GTPases, RagA and RagB, are required for the HIV-1-mediated LEL repositioning that is likely mediated by interactions between the ..
  9. Kreutz D, Sinthuvanich C, Bileck A, Janker L, Muqaku B, Slany A, et al. Curcumin exerts its antitumor effects in a context dependent fashion. J Proteomics. 2018;182:65-72 pubmed publisher
    ..In the ZR-75-1/CLC co-culture, curcumin significantly down-regulated PEG10, an anti-apoptotic protein, and induced RRAGA, a pro-apoptotic protein involved in TNF-alpha signaling...
  10. Tao R, Xiong X, Liangpunsakul S, Dong X. Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling. Diabetes. 2015;64:1211-23 pubmed publisher
    ..suggests that sestrins may inhibit mTORC1 (mechanistic target of rapamycin complex 1) through inhibition of RagA/B GTPases or activation of AMPK; however, whether sestrins are also involved in mTORC2 regulation and function is ..
  11. Megat S, Ray P, Moy J, Lou T, Barragán Iglesias P, Li Y, et al. Nociceptor Translational Profiling Reveals the Ragulator-Rag GTPase Complex as a Critical Generator of Neuropathic Pain. J Neurosci. 2019;39:393-411 pubmed publisher
    ..b>RagA, a GTPase controlling mTORC1 activity, is identified as a novel target of MNK1-eIF4E signaling...
  12. 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 ..
  13. Glew M, Veith P, Chen D, Seers C, Chen Y, Reynolds E. Blue native-PAGE analysis of membrane protein complexes in Porphyromonas gingivalis. J Proteomics. 2014;110:72-92 pubmed publisher
    ..b>RagA and RagB were observed in three different complex sizes...
  14. Lackford B, Yao C, Charles G, Weng L, Zheng X, Choi E, et al. Fip1 regulates mRNA alternative polyadenylation to promote stem cell self-renewal. EMBO J. 2014;33:878-89 pubmed publisher
    ..Here, we show that an mRNA 3' processing factor, Fip1, is essential for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming...
  15. Laufenberg L, Pruznak A, Navaratnarajah M, Lang C. Sepsis-induced changes in amino acid transporters and leucine signaling via mTOR in skeletal muscle. Amino Acids. 2014;46:2787-98 pubmed publisher
    ..There was no sepsis or Leu effect on the protein content for RagA-D, LAMTOR-1 and -2, raptor, Rheb or mTOR in muscle...
  16. Andres M, Pulis E, Cribb T, Overstreet R. Erection of the haploporid genus Litosaccus n. g. and its phylogenetic relationship within the Haploporidae Nicoll, 1914. Syst Parasitol. 2014;89:185-94 pubmed publisher
    ..It also resembles Pseudolecithobotrys Blasco-Costa, Gibson, Balbuena, Raga & Kostadinova, 2009, but the only member of that genus has a hermaphroditic sac that is twice the length of the ..
  17. Ho C, Wang J, Lee C, Cheng H, Wen W, Cheng H, et al. Antroquinonol blocks Ras and Rho signaling via the inhibition of protein isoprenyltransferase activity in cancer cells. Biomed Pharmacother. 2014;68:1007-14 pubmed publisher
  18. Wolfson R, Chantranupong L, Wyant G, Gu X, Orozco J, Shen K, et al. KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1. Nature. 2017;543:438-442 pubmed publisher
    ..complexes regulate the Rag GTPases in response to amino acids, including GATOR1, a GTPase activating protein for RAGA, and GATOR2, a positive regulator of unknown molecular function...
  19. Li W, You B, Hoque M, Zheng D, Luo W, Ji Z, et al. Systematic profiling of poly(A)+ transcripts modulated by core 3' end processing and splicing factors reveals regulatory rules of alternative cleavage and polyadenylation. PLoS Genet. 2015;11:e1005166 pubmed publisher
    ..Whereas Pcf11 and Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1 and PABPC1 promote usage of distal pAs...
  20. Kira S, Kumano Y, Ukai H, Takeda E, Matsuura A, Noda T. Dynamic relocation of the TORC1-Gtr1/2-Ego1/2/3 complex is regulated by Gtr1 and Gtr2. Mol Biol Cell. 2016;27:382-96 pubmed publisher
    ..and autophagy by integrating various signals, including nutrient availability, through the small GTPases RagA/B/C/D in mammals and Gtr1/2 in budding yeast...
  21. Jewell J, Kim Y, Russell R, Yu F, Park H, Plouffe S, et al. Metabolism. Differential regulation of mTORC1 by leucine and glutamine. Science. 2015;347:194-8 pubmed publisher
    ..Glutamine promoted mTORC1 translocation to the lysosome in RagA and RagB knockout cells and required the v-ATPase but not the Ragulator...
  22. Meng J, Ferguson S. GATOR1-dependent recruitment of FLCN-FNIP to lysosomes coordinates Rag GTPase heterodimer nucleotide status in response to amino acids. J Cell Biol. 2018;217:2765-2776 pubmed publisher
    ..FLCN is recruited to lysosomes during amino acid starvation, where it interacts with RagA/B as a heterodimeric complex with FLCN-interacting proteins (FNIPs)...
  23. Clerici M, Faini M, Aebersold R, Jinek M. Structural insights into the assembly and polyA signal recognition mechanism of the human CPSF complex. elife. 2017;6: pubmed publisher
    ..A core CPSF complex comprising CPSF160, WDR33, CPSF30 and Fip1 is sufficient for AAUAAA motif recognition, yet the molecular interactions underpinning its assembly and mechanism ..
  24. Carson B, Del Bas J, Moreno Navarrete J, Fernandez Real J, Mora S. The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion. PLoS ONE. 2013;8:e74687 pubmed publisher
    ..Overexpression of wild type rab11 FIP1, FIP3 and FIP5 decreased the amount of secreted adiponectin expressed in HEK293 cells, whereas overexpression of ..
  25. 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
    ..The GTP-GDP cycle of the RagD-RagB pair, rather than the RagC-RagA pair, is critical for leucine-induced mTORC1 activation...
  26. Shen K, Sidik H, Talbot W. The Rag-Ragulator Complex Regulates Lysosome Function and Phagocytic Flux in Microglia. Cell Rep. 2016;14:547-559 pubmed publisher
    ..We show that RagA and Lamtor4, two components of the Rag-Ragulator complex, are essential regulators of lysosomes in microglia...
  27. Kim J, Kim E. Rag GTPase in amino acid signaling. Amino Acids. 2016;48:915-28 pubmed publisher
    ..Compelling evidence suggests that Rag heterodimer (RagA/B and RagC/D) plays an important role in amino acid signaling toward mechanistic target of rapamycin complex 1 (..
  28. 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
    ..through a variety of sensors and regulators 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...
  29. Jin S, Liao Q, Chen J, Zhang L, He Q, Zhu H, et al. TSC1 and DEPDC5 regulate HIV-1 latency through the mTOR signaling pathway. Emerg Microbes Infect. 2018;7:138 pubmed publisher
    ..that TSC1 suppresses AKT-mTORC1-S6 via downregulation of Rheb, whereas DEPDC5 inhibits AKT-mTORC1-S6 through RagA. Overall, both TSC1 and DEPDC5 negatively regulate the AKT-mTORC1 pathway, and thus their agonists could be used in ..
  30. Fraija Fernández N, Aznar F, Raga J, Gibson D, Fernández M. A new brachycladiid species (Digenea) from Gervais' beaked whale Mesoplodon europaeus in north-western Atlantic waters. Acta Parasitol. 2014;59:510-7 pubmed publisher
    ..atlanticum (Abril, Balbuena and Raga, 1991) Gibson, 2005, considered the morphologically closest species...
  31. Schwer B, Bitton D, Sanchez A, Bähler J, Shuman S. Individual letters of the RNA polymerase II CTD code govern distinct gene expression programs in fission yeast. Proc Natl Acad Sci U S A. 2014;111:4185-90 pubmed publisher
    ..Y1F and S2A elicited increased expression of genes encoding proteins involved in iron uptake (Frp1, Fip1, Fio1, Str3, Str1, Sib1), without affecting the expression of the genes that repress the iron regulon, implying ..
  32. 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...
  33. Suryawan A, Davis T. Amino Acid- and Insulin-Induced Activation of mTORC1 in Neonatal Piglet Skeletal Muscle Involves Sestin2-GATOR2, Rag A/C-mTOR, and RHEB-mTOR Complex Formation. J Nutr. 2018;148:825-833 pubmed publisher
    ..05) compared with control in 26- but not in 6-d-old pigs. Formation of Ras-related GTP-binding protein A (RagA)-mTOR, RagC-mTOR, and Ras homolog enriched in brain (RHEB)-mTOR complexes was increased (P < 0...
  34. Chen C, Ho S, Kuo T, Hsieh H, Cheng Y. Structural basis of jasmonate-amido synthetase FIN219 in complex with glutathione S-transferase FIP1 during the JA signal regulation. Proc Natl Acad Sci U S A. 2017;114:E1815-E1824 pubmed publisher
    ..of jasmonoyl-isoleucine in JA-mediated defense responses and interacts with FIN219-interacting protein 1 (FIP1) under FR light conditions...
  35. Chakrabarti M, Dinkins R, Hunt A. Genome-wide atlas of alternative polyadenylation in the forage legume red clover. Sci Rep. 2018;8:11379 pubmed publisher
    ..genes encoding different poly(A) factors showed significant differential expression of genes encoding orthologs of FIP1(V) and PCFS4, suggesting that these two factors may play a role in regulating spatial APA in red clover...
  36. Kunikullaya K, Goturu J, Muradi V, Hukkeri P, Kunnavil R, Doreswamy V, et al. Combination of music with lifestyle modification versus lifestyle modification alone on blood pressure reduction - A randomized controlled trial. Complement Ther Clin Pract. 2016;23:102-9 pubmed publisher
    ..Both the groups were given lifestyle modifications while one had added music intervention (raga bhimpalas) for 3 months...
  37. Shen K, Huang R, Brignole E, Condon K, Valenstein M, Chantranupong L, et al. Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes. Nature. 2018;556:64-69 pubmed publisher
    ..complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of GATOR1 desensitizes mTORC1 signalling to nutrient starvation...
  38. García Varela M, Henández Orts J, Pinacho Pinacho C. A morphological and molecular study of Pseudocorynosoma Aznar, Pérez Ponce de León and Raga 2006 (Acanthocephala: Polymorphidae) from Mexico with the description of a new species and the presence of cox 1 pseudogenes. Parasitol Int. 2017;66:27-36 pubmed publisher
    ..The morphological evidence, plus the monophyly in both phylogenetic analyses indicate that the acanthocephalans collected from intestine of the ruddy duck from northern Mexico represent a new species. ..
  39. Wu Y, Li B, Zhao M, Mitchell L, Xie Z, Lin Q, et al. Bug mapping and fitness testing of chemically synthesized chromosome X. Science. 2017;355: pubmed publisher
    ..that included a large region bearing complex amplifications, a growth defect mapping to a recoded sequence in FIP1, and a loxPsym site affecting promoter function of ATP2 PoPM is a powerful tool for synthetic yeast ..
  40. Zhang J, Kong R, Sun L. Silencing of Rab3D suppresses the proliferation and invasion of esophageal squamous cell carcinoma cells. Biomed Pharmacother. 2017;91:402-407 pubmed publisher
    ..Overall, these findings suggest that targeting the Rab3D may be a potential therapeutic target for treatment of ESCC. ..
  41. Kunikullaya K, Goturu J, Muradi V, Hukkeri P, Kunnavil R, Doreswamy V, et al. Music versus lifestyle on the autonomic nervous system of prehypertensives and hypertensives--a randomized control trial. Complement Ther Med. 2015;23:733-40 pubmed publisher
    ..The objective of this study was to evaluate the effect of passive listening to relaxing raga on the autonomic functions of hypertensives and prehypertensives and provide scientific evidence...
  42. 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)...
  43. Zhu Y, Wang X, Forouzmand E, Jeong J, Qiao F, Sowd G, et al. Molecular Mechanisms for CFIm-Mediated Regulation of mRNA Alternative Polyadenylation. Mol Cell. 2018;69:62-74.e4 pubmed publisher
    ..arginine-serine repeat (RS) domains of CFIm68/59, which bind specifically to an RS-like region in the CPSF subunit Fip1, and this interaction is inhibited by CFIm68/59 hyper-phosphorylation...
  44. Rinaldi F, Packer M, Collins R. New insights into the molecular mechanism of the Rab GTPase Sec4p activation. BMC Struct Biol. 2015;15:14 pubmed publisher
    ..Understanding the structural properties of mutants such as the one described here, provides useful insights into unique aspects of Rab GTPase function. ..
  45. Ma N, Ma Y, Nakashima A, Kikkawa U, Furuyashiki T. The Loss of Lam2 and Npr2-Npr3 Diminishes the Vacuolar Localization of Gtr1-Gtr2 and Disinhibits TORC1 Activity in Fission Yeast. PLoS ONE. 2016;11:e0156239 pubmed publisher
    ..It is thought that the Ragulator complex and the GATOR (GAP activity towards Rags) complex regulate RagA/B as its GDP/GTP exchange factor (GEF) and GTPase-activating protein (GAP), respectively...
  46. Heintz C, Doktor T, Lanjuin A, Escoubas C, Zhang Y, Weir H, et al. Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans. Nature. 2017;541:102-106 pubmed publisher
    ..required for lifespan extension by dietary restriction and by modulation of the TORC1 pathway components AMPK, RAGA-1 and RSKS-1/S6 kinase. We also demonstrate that overexpression of SFA-1 is sufficient to extend lifespan...
  47. Han M, Huang B, Chen A, Zhang X, Xu R, Wang J, et al. High expression of RAB43 predicts poor prognosis and is associated with epithelial-mesenchymal transition in gliomas. Oncol Rep. 2017;37:903-912 pubmed publisher
    ..In conclusion, a high level of RAB43 was significantly associated with the malignant phenotypes of gliomas, which suggests that RAB43 may serve as a novel biomarker and a potential therapeutic target for gliomas. ..
  48. Milkereit R, Persaud A, Vanoaica L, Guetg A, Verrey F, Rotin D. LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation. Nat Commun. 2015;6:7250 pubmed publisher
    ..V-ATPase stimulation by intra-lysosomal EAA (inside-out activation), leading to activation of the Ragulator, RagA/B-GTP and mTORC1 via Rheb-GTP. How Leu enters the lysosomes is unknown...
  49. Kimball S, Ravi S, Gordon B, Dennis M, Jefferson L. Amino Acid-Induced Activation of mTORC1 in Rat Liver Is Attenuated by Short-Term Consumption of a High-Fat Diet. J Nutr. 2015;145:2496-502 pubmed publisher
    ..rather to resistance to amino acid-induced activation of mTORC1, as evidenced by a reduction in the interaction of RagA (69% of CON) and RagC (66% of CON) with mTOR and enhanced expression of the mTORC1 repressors Sestrin2 (132% of CON)..
  50. Andrzejewska Z, Nevo N, Thomas L, Chhuon C, Bailleux A, Chauvet V, et al. Cystinosin is a Component of the Vacuolar H+-ATPase-Ragulator-Rag Complex Controlling Mammalian Target of Rapamycin Complex 1 Signaling. J Am Soc Nephrol. 2016;27:1678-88 pubmed publisher
    ..of vacuolar H(+)-ATPase and the Ragulator complex and with the small GTPases Ras-related GTP-binding protein A (RagA) and RagC...
  51. 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
    ..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...
  52. Boutry C, El Kadi S, Suryawan A, Steinhoff Wagner J, Stoll B, Orellana R, et al. Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs. Am J Physiol Endocrinol Metab. 2016;310:E699-E713 pubmed publisher
    ..no treatment effects on PKB, eIF2α, eEF2, or PRAS40 phosphorylation, Rheb, SLC38A9, v-ATPase, LAMTOR1, LAMTOR2, RagA, RagC, and LAT1 abundance, the proportion of polysomes to nonpolysomes, or the proportion of mRNAs encoding rpS4 or ..
  53. Peng M, Yin N, Li M. SZT2 dictates GATOR control of mTORC1 signalling. Nature. 2017;543:433-437 pubmed publisher
    ..regulates mTORC1 signalling through Rag GTPases, and GATOR1 displays GTPase activating protein (GAP) activity for RAGA and RAGB (RAGA/B) and GATOR2 has been proposed to be an inhibitor of GATOR1...
  54. Ferroni L, Gardin C, Dolkart O, Salai M, Barak S, Piattelli A, et al. Pulsed electromagnetic fields increase osteogenetic commitment of MSCs via the mTOR pathway in TNF-α mediated inflammatory conditions: an in-vitro study. Sci Rep. 2018;8:5108 pubmed publisher
    ..that PEMFs contribute to activation of the mTOR pathway via upregulation of the proteins AKT, MAPP kinase, and RRAGA, suggesting that activation of the mTOR pathway is required for PEMF-stimulated osteogenic differentiation...
  55. Fingar D. Rag Ubiquitination Recruits a GATOR1: Attenuation of Amino Acid-Induced mTORC1 Signaling. Mol Cell. 2015;58:713-5 pubmed publisher
    In recent issues of Molecular Cell, two reports identify that K63-linked RagA polyubiquitination and subsequent recruitment of GATOR1, a complex with GAP activity toward RagA/B GTPases, can attenuate amino acid-induced mTORC1 signaling.
  56. Zhang X, Zhang Y, Yang J, Li S, Chen J. Upregulation of miR-582-5p inhibits cell proliferation, cell cycle progression and invasion by targeting Rab27a in human colorectal carcinoma. Cancer Gene Ther. 2015;22:475-80 pubmed publisher
    ..Our data suggest that miR-582-5p may function as a tumor suppressor in the development of CRC by targeting Rab27a, indicating a novel therapeutic strategy for patients with CRC. ..
  57. Palacios Abella J, Georgieva S, Mele S, Raga J, Isbert W, Kostadinova A, et al. Skoulekia erythrini n. sp. (Digenea: Aporocotylidae): a parasite of Pagellus erythrinus (L.) (Perciformes: Sparidae) from the western Mediterranean with an amendment of the generic diagnosis. Syst Parasitol. 2017;94:669-688 pubmed publisher
    ..The new species differs from the type- and only species of the genus, S. meningialis Alama-Bermejo, Montero, Raga & Holzer, 2011 in possessing a symmetrical body (vs laterally curved), short tegumental spines (3-4 vs 7-10 ..
  58. Merino Gracia J, Zamora Carreras H, Bruix M, Rodríguez Crespo I. Molecular Basis for the Protein Recognition Specificity of the Dynein Light Chain DYNLT1/Tctex1: CHARACTERIZATION OF THE INTERACTION WITH ACTIVIN RECEPTOR IIB. J Biol Chem. 2016;291:20962-20975 pubmed
    ..chains to subsequently link cargo proteins such as the guanine nucleotide exchange factor Lfc or the small GTPases RagA and Rab3D...
  59. Kalaitzidis D, Lee D, Efeyan A, Kfoury Y, Nayyar N, Sykes D, et al. Amino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells. J Clin Invest. 2017;127:1405-1413 pubmed publisher
    ..Amino acids or glucose facilitates mTORC1 activation by inducing RagA GTPase recruitment of mTORC1 to the lysosomal outer surface, enabling activation of mTOR by the Ras homolog Rheb...
  60. Wang S, Tsun Z, Wolfson R, Shen K, Wyant G, Plovanich M, et al. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science. 2015;347:188-94 pubmed publisher
    ..Thus, SLC38A9 functions upstream of the Rag GTPases and is an excellent candidate for being an arginine sensor for the mTORC1 pathway. ..
  61. Kwon O, Kwak D, Ha S, Jeon H, Park M, Chang Y, et al. Nudix-type motif 2 contributes to cancer proliferation through the regulation of Rag GTPase-mediated mammalian target of rapamycin complex 1 localization. Cell Signal. 2017;32:24-35 pubmed publisher
    ..Taken together, these results show that NUDT2 is a novel complex formation enhancing factor regulating mTORC1-Rag GTPase signaling that is crucial for cell growth control. ..
  62. Li B, Zhang G, Li C, Li R, Lu J, He Z, et al. Lyn mediates FIP1L1-PDGFRA signal pathway facilitating IL-5RA intracellular signal through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex in CEL. Oncotarget. 2017;8:64984-64998 pubmed publisher
    The Fip1-like1 (FIP1L1)-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) oncogene can cause chronic eosinophilic leukemia (CEL), but requires IL-5 cytokine participation...
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    ..Thus SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR. ..
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    ..Here we report the crystal structure of Ragulator in complex with the roadblock domains of RagA-C, which helps to elucidate the molecular basis for the regulation of Rag GTPases...
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    ..Glutaminylation on apoptosis signal-regulating kinase 1 suppresses apoptosis. We discovered non-canonical functions of ARSs and revealed systematic and functional amino acid sensing and signal transduction networks. ..
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    ..Interestingly, p62 colocalizes with Rags at the lysosomal compartment and is required for the interaction of mTOR with Rag GTPases in vivo and for translocation of the mTORC1 complex to the lysosome, a crucial step for mTOR activation. ..
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    ..lysosome-anchored E3 ubiquitin ligase RNF152 as an essential negative regulator of the mTORC1 pathway by targeting RagA for K63-linked ubiquitination. RNF152 interacts with and ubiquitinates RagA in an amino-acid-sensitive manner...
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    ..We have analysed in detail how RagA, another small GTPase, associates to DYNLT...
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    cDNA clones of two novel Ras-related GTP-binding proteins (RagA and RagB) were isolated from rat and human cDNA libraries...
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  73. Li T, Yeung J, Li J, Zhang Y, Melody T, Gao Y, et al. Comparison of regional with general anaesthesia on postoperative delirium (RAGA-delirium) in the older patients undergoing hip fracture surgery: study protocol for a multicentre randomised controlled trial. BMJ Open. 2017;7:e016937 pubmed publisher
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    ..These results demonstrate that SH3BP4 is a negative regulator of the Rag GTPase complex and amino acid-dependent mTORC1 signaling. ..
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    ..In addition, we found that MARK4 phosphorylates Raptor, a key component of mTORC1, and this phosphorylation may interfere with Raptor-Rag interaction. Our data demonstrate MARK4 as a new negative regulator of mTORC1. ..
  76. Wu L, Zhou B, Oshiro Rapley N, Li M, Paulo J, Webster C, et al. An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer. Cell. 2016;167:1705-1718.e13 pubmed publisher
    ..that biguanides inhibit growth by inhibiting mitochondrial respiratory capacity, which restrains transit of the RagA-RagC GTPase heterodimer through the NPC...
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    ..EM was used to reconstruct the assembly of the full-length RagAGTP:RagCGDP dimer bound to Ragulator at 16 Å resolution, revealing that the G-domains of the ..
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    ..GATOR1 serves as an mTORC1 inhibitor and activates the mTORC1-modulating RagA GTPase. However, several GATOR members have mTORC1 independent functions...
  79. Li Y, Kang J, Horwitz M. Interaction of an adenovirus 14.7-kilodalton protein inhibitor of tumor necrosis factor alpha cytolysis with a new member of the GTPase superfamily of signal transducers. J Virol. 1997;71:1576-82 pubmed
    ..FIP-1 has two consensus sequences for myristoylation which would be expected to facilitate membrane association and also has sequences for Ser/Thr as well as Tyr phosphorylation that could affect its function. ..
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    ..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...
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    ..protein, which inhibits mTORC1 signaling by interacting with GATOR1, the GTPase activating protein (GAP) for RagA/B...
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    ..Instead, dynasore inhibited RagA binding to Raptor, reduced mTORC1 recruitment to the lysosome, and inhibited Akt activation and TSC2-S939 ..
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    ..Amino-acid-induced activation of mammalian TORC1 is initiated by its recruitment to the RagA/B-RagC/D GTPase heterodimer, which is anchored to lysosomal membranes through the Ragulator complex...
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    ..Based on sequence similarity to the Saccharomyces cerevisiae polyadenylation factor Fip1p, we have identified human Fip1 (hFip1) and found that the protein is an integral subunit of CPSF...
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    ..Abc3 was required for growth in low-iron medium in the absence of the transport system mediated by Fio1 and Fip1. abc3Delta cells exhibited increased levels of expression of the frp1(+)-encoded ferric reductase, suggesting a ..
  86. Chen J, Huang C, Zhang B, Yin S, Liang J, Xu C, et al. Mutations of RagA GTPase in mTORC1 Pathway Are Associated with Autosomal Dominant Cataracts. PLoS Genet. 2016;12:e1006090 pubmed publisher
    ..Herein, we report that mutations in the RagA GTPase (RRAGA), a key regulator of the mechanistic rapamycin complex 1 (mTORC1), are associated with autosomal dominant ..
  87. Shen K, Choe A, Sabatini D. Intersubunit Crosstalk in the Rag GTPase Heterodimer Enables mTORC1 to Respond Rapidly to Amino Acid Availability. Mol Cell. 2017;68:552-565.e8 pubmed publisher
    ..Thus, the dynamic response of mTORC1 requires intersubunit communication by the Rag GTPases, providing a rationale for why they exist as a dimer and revealing a distinct mode of control for a GTP-binding protein. ..
  88. Hirose E, Nakashima N, Sekiguchi T, Nishimoto T. RagA is a functional homologue of S. cerevisiae Gtr1p involved in the Ran/Gsp1-GTPase pathway. J Cell Sci. 1998;111 ( Pt 1):11-21 pubmed
    Human RagA and RagB is reported to be 52% identical to a putative GTPase of Saccharomyces cerevisiae, Gtr1p...
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    The regulation of RagA(GTP) is important for amino-acid-induced mTORC1 activation...
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    ..Mutation of the Rag P-loop corresponding to Ras(Ser-17) abolishes guanyl nucleotide binding. Such a mutation in RagA or RagB inhibits, whereas in RagC or RagD it enhances, Rag heterodimer binding to mTORC1...