RHEB

Summary

Gene Symbol: RHEB
Description: Ras homolog, mTORC1 binding
Alias: RHEB2, GTP-binding protein Rheb, Ras homolog enriched in brain 2
Species: human
Products:     RHEB

Top Publications

  1. Flinn R, Yan Y, Goswami S, Parker P, Backer J. The late endosome is essential for mTORC1 signaling. Mol Biol Cell. 2010;21:833-41 pubmed publisher
    ..Inhibition of other stages of endocytic trafficking had no effect on mTORC1. Overexpression of Rheb, which activates mTOR independently of mTOR localization, rescued mTORC1 signaling in cells expressing Rab5CA, ..
  2. Li Y, Wang Y, Kim E, Beemiller P, Wang C, Swanson J, et al. Bnip3 mediates the hypoxia-induced inhibition on mammalian target of rapamycin by interacting with Rheb. J Biol Chem. 2007;282:35803-13 pubmed
    ..b>Rheb, a Ras-related small GTPase, is a key upstream activator of mTOR...
  3. Clark G, Kinch M, Rogers Graham K, Sebti S, Hamilton A, Der C. The Ras-related protein Rheb is farnesylated and antagonizes Ras signaling and transformation. J Biol Chem. 1997;272:10608-15 pubmed
    Presently, nothing is known about the function of the Ras-related protein Rheb. Since Rheb shares significant sequence identity with the core effector domains of Ras and KRev-1/Rap1A, it may share functional similarities with these two ..
  4. Kim S, Chen X, Oo T, Kareva T, Yarygina O, Wang C, et al. Dopaminergic pathway reconstruction by Akt/Rheb-induced axon regeneration. Ann Neurol. 2011;70:110-20 pubmed publisher
    ..nigra (SN) with constitutively active forms of the kinase Akt and the GTPase Ras homolog enriched in brain (Rheb) to induce regrowth of axons after they have been destroyed by neurotoxin lesion...
  5. Long X, Lin Y, Ortiz Vega S, Yonezawa K, Avruch J. Rheb binds and regulates the mTOR kinase. Curr Biol. 2005;15:702-13 pubmed
    ..Genetic evidence establishes that TOR complex activity in vivo requires the small GTPase Rheb, and overexpression of Rheb can rescue TOR from inactivation in vivo by amino-acid withdrawal...
  6. Bai X, Ma D, Liu A, Shen X, Wang Q, Liu Y, et al. Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38. Science. 2007;318:977-80 pubmed
    The mammalian target of rapamycin, mTOR, is a central regulator of cell growth. Its activity is regulated by Rheb, a Ras-like small guanosine triphosphatase (GTPase), in response to growth factor stimulation and nutrient availability...
  7. Basso A, Mirza A, Liu G, Long B, Bishop W, Kirschmeier P. The farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling. Role in FTI enhancement of taxane and tamoxifen anti-tumor activity. J Biol Chem. 2005;280:31101-8 pubmed
    ..We found that Rheb and Rheb2 mRNA were elevated in various tumor cell lines relative to normal cells...
  8. Garami A, Zwartkruis F, Nobukuni T, Joaquin M, Roccio M, Stocker H, et al. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol Cell. 2003;11:1457-66 pubmed
    ..Here we provide evidence that TSC1/2 is a GAP for the small GTPase Rheb and that insulin-mediated Rheb activation is PI3K dependent...
  9. Yu Y, Li S, Xu X, Li Y, Guan K, Arnold E, et al. Structural basis for the unique biological function of small GTPase RHEB. J Biol Chem. 2005;280:17093-100 pubmed
    The small GTPase Rheb displays unique biological and biochemical properties different from other small GTPases and functions as an important mediator between the tumor suppressor proteins TSC1 and TSC2 and the mammalian target of ..

More Information

Publications84

  1. Karbowniczek M, Cash T, Cheung M, Robertson G, Astrinidis A, Henske E. Regulation of B-Raf kinase activity by tuberin and Rheb is mammalian target of rapamycin (mTOR)-independent. J Biol Chem. 2004;279:29930-7 pubmed
    ..Expression of Rheb, the target of the GTPase-activating domain of tuberin, inhibited wild-type B-Raf kinase but not activated forms of ..
  2. Nardella C, Chen Z, Salmena L, Carracedo A, Alimonti A, Egia A, et al. Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events. Genes Dev. 2008;22:2172-7 pubmed publisher
    ..We report here that Rheb GTPase, the upstream activator of the mTOR complex 1 (mTORC1) is amplified in human prostate cancers...
  3. Tee A, Blenis J, Proud C. Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1. FEBS Lett. 2005;579:4763-8 pubmed
    The small G protein Rheb (Ras homologue enriched in brain) is known to promote mammalian target of rapamycin (mTOR) signaling...
  4. Yamagata K, Sanders L, Kaufmann W, Yee W, Barnes C, Nathans D, et al. rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel Ras-related protein. J Biol Chem. 1994;269:16333-9 pubmed
    ..Here we describe an inducible novel member of the Ras family of small GTP-binding proteins we have termed Rheb. rheb mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by NMDA-dependent ..
  5. Mavrakis K, Zhu H, Silva R, Mills J, Teruya Feldstein J, Lowe S, et al. Tumorigenic activity and therapeutic inhibition of Rheb GTPase. Genes Dev. 2008;22:2178-88 pubmed publisher
    ..We find that Rheb, a proximal activator of mTORC1, can produce rapid development of aggressive and drug-resistant lymphomas...
  6. Kita K, Wu Y, Sugaya S, Moriya T, Nomura J, Takahashi S, et al. Search for UV-responsive genes in human cells by differential mRNA display: involvement of human ras-related GTP-binding protein, Rheb, in UV susceptibility. Biochem Biophys Res Commun. 2000;274:859-64 pubmed
    ..Messenger RNA expression levels of human Ras homologue enriched in brain (Rheb) and/or a Rheb-like gene were up-regulated and slightly decreased in UV-irradiated RSa and UV(r)-1 cells, compared ..
  7. Long X, Ortiz Vega S, Lin Y, Avruch J. Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J Biol Chem. 2005;280:23433-6 pubmed
    ..This inhibition can be overcome by overexpression of the Rheb GTPase...
  8. Ma D, Bai X, Zou H, Lai Y, Jiang Y. Rheb GTPase controls apoptosis by regulating interaction of FKBP38 with Bcl-2 and Bcl-XL. J Biol Chem. 2010;285:8621-7 pubmed publisher
    ..The inhibitory action of FKBP38 is antagonized by Rheb, an oncogenic small GTPase, which interacts with FKBP38 and prevents its association with mTOR...
  9. Hanker A, Mitin N, Wilder R, Henske E, Tamanoi F, Cox A, et al. Differential requirement of CAAX-mediated posttranslational processing for Rheb localization and signaling. Oncogene. 2010;29:380-91 pubmed publisher
    The Rheb1 and Rheb2 small GTPases and their effector mTOR are aberrantly activated in human cancer and are attractive targets for anti-cancer drug discovery...
  10. Ma D, Bai X, Guo S, Jiang Y. The switch I region of Rheb is critical for its interaction with FKBP38. J Biol Chem. 2008;283:25963-70 pubmed publisher
    The Ras-like small GTPase Rheb is an upstream activator of the mammalian target of rapamycin (mTOR)...
  11. Saito K, Araki Y, Kontani K, Nishina H, Katada T. Novel role of the small GTPase Rheb: its implication in endocytic pathway independent of the activation of mammalian target of rapamycin. J Biochem. 2005;137:423-30 pubmed
    The Ras-homologous GTPase Rheb that is conserved from yeast to human appears to be involved not only in cell growth but also in nutrient uptake...
  12. Inoki K, Li Y, Xu T, Guan K. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 2003;17:1829-34 pubmed
    ..Here we report that TSC2 is a GTPase-activating protein (GAP) toward Rheb, a Ras family GTPase. Rheb stimulates phosphorylation of S6K and 4EBP1...
  13. Zhang Y, Gao X, Saucedo L, Ru B, Edgar B, Pan D. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat Cell Biol. 2003;5:578-81 pubmed
    ..Here we show that the small GTPase Rheb (Ras homologue enriched in brain) is a direct target of Tsc2 GAP activity both in vivo and in vitro...
  14. Gromov P, Madsen P, Tomerup N, Celis J. A novel approach for expression cloning of small GTPases: identification, tissue distribution and chromosome mapping of the human homolog of rheb. FEBS Lett. 1995;377:221-6 pubmed
    ..procedure we have cloned several small GTP-binding proteins from human keratinocytes including the human homolog of rheb, a novel member of the ras-related GTP-binding proteins...
  15. Buerger C, DeVries B, Stambolic V. Localization of Rheb to the endomembrane is critical for its signaling function. Biochem Biophys Res Commun. 2006;344:869-80 pubmed
    b>Rheb, a small GTPase, has emerged as a key molecular switch that directly regulates the activity of the mammalian target of rapamycin (mTOR)...
  16. Maehama T, Tanaka M, Nishina H, Murakami M, Kanaho Y, Hanada K. RalA functions as an indispensable signal mediator for the nutrient-sensing system. J Biol Chem. 2008;283:35053-9 pubmed publisher
    ..In addition, RalA knockdown suppressed Rheb-induced S6 kinase phosphorylation, and the constitutively active form of RalA induced mTORC1 activation in the ..
  17. Tee A, Manning B, Roux P, Cantley L, Blenis J. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol. 2003;13:1259-68 pubmed
    ..We show that the small G protein Rheb (Ras homolog enriched in brain) is a molecular target of TSC1/TSC2 that regulates mTOR signaling...
  18. Berghaus C, Schwarten M, Heumann R, Stoll R. Sequence-specific 1H, 13C, and 15N backbone assignment of the GTPase rRheb in its GDP-bound form. Biomol NMR Assign. 2007;1:45-7 pubmed publisher
    b>Rheb (Ras homologue enriched in brain) is a small GTPase that plays an important role in tuberous sclerosis. Here we present the backbone assignments of rRheb in its GDP-bound state...
  19. Karassek S, Berghaus C, Schwarten M, Goemans C, Ohse N, Kock G, et al. Ras homolog enriched in brain (Rheb) enhances apoptotic signaling. J Biol Chem. 2010;285:33979-91 pubmed publisher
    b>Rheb is a homolog of Ras GTPase that regulates cell growth, proliferation, and regeneration via mammalian target of rapamycin (mTOR)...
  20. Yee W, Worley P. Rheb interacts with Raf-1 kinase and may function to integrate growth factor- and protein kinase A-dependent signals. Mol Cell Biol. 1997;17:921-33 pubmed
    b>Rheb is a recently described member of the Ras family that was originally identified as an immediate-early gene in brain but is also widely expressed in other tissues...
  21. 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
    ..amino acids by promoting mTORC1 translocation to a membrane-bound compartment that contains the mTORC1 activator, Rheb. We show that amino acids induce the movement of mTORC1 to lysosomal membranes, where the Rag proteins reside...
  22. Castro A, Rebhun J, Clark G, Quilliam L. Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner. J Biol Chem. 2003;278:32493-6 pubmed
    ..TSC2 was found to bind to Rheb-GTP in vitro and to reduce Rheb GTP levels in vivo...
  23. Jiang H, Vogt P. Constitutively active Rheb induces oncogenic transformation. Oncogene. 2008;27:5729-40 pubmed publisher
    b>Rheb (Ras-homolog enriched in brain) is a component of the phosphatidylinositol 3-kinase (PI3K) target of rapamycin (TOR) signaling pathway, functioning as a positive regulator of TOR...
  24. Li Y, Werner H, Püschel A. Rheb and mTOR regulate neuronal polarity through Rap1B. J Biol Chem. 2008;283:33784-92 pubmed publisher
    ..Here we show that PI3K regulates axon specification and elongation through the GTPase Rheb and its target mammalian target of rapamycin (mTOR)...
  25. Karbowniczek M, Robertson G, Henske E. Rheb inhibits C-raf activity and B-raf/C-raf heterodimerization. J Biol Chem. 2006;281:25447-56 pubmed
    ..We have recently shown that B-Raf kinase interacts with and is inhibited by Rheb, the target of the GTPase-activating domain of the tuberous sclerosis complex 2 gene product tuberin...
  26. Rhee S, Bae S. The antioxidant function of sestrins is mediated by promotion of autophagic degradation of Keap1 and Nrf2 activation and by inhibition of mTORC1. Free Radic Biol Med. 2015;88:205-211 pubmed publisher
    ..either via the AMPK-dependent phosphorylation and activation of TSC2 and consequent inhibition of the GTPase Rheb or via inhibition of the GTPase Rag and consequent prevention of the lysosomal localization of mTORC1 triggered by ..
  27. You J, Anderson G, Dooley M, Hornberger T. The role of mTOR signaling in the regulation of protein synthesis and muscle mass during immobilization in mice. Dis Model Mech. 2015;8:1059-69 pubmed publisher
    ..Similar to isometric contractions, overexpression of Rheb in immobilized muscles enhanced mTOR signaling, cap-dependent translation and global protein synthesis, and ..
  28. Mazhab Jafari M, Marshall C, Ho J, Ishiyama N, Stambolic V, Ikura M. Structure-guided mutation of the conserved G3-box glycine in Rheb generates a constitutively activated regulator of mammalian target of rapamycin (mTOR). J Biol Chem. 2014;289:12195-201 pubmed publisher
    ..g. Rap) or not catalytic (e.g. Rheb)...
  29. Neuman N, Henske E. Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis. EMBO Mol Med. 2011;3:189-200 pubmed publisher
    ..TSC) genes, TSC1 and TSC2, form a complex, which inhibits the small G-protein, Ras homolog enriched in brain (Rheb)...
  30. Sucher N, Yu E, Chan S, Miri M, Lee B, Xiao B, et al. Association of the small GTPase Rheb with the NMDA receptor subunit NR3A. Neurosignals. 2010;18:203-9 pubmed publisher
    ..Using a yeast two-hybrid system, we identified the mTOR-activating GTPase Rheb as an interacting protein of the NMDAR subunit NR3A...
  31. Yang H, Jiang X, Li B, Yang H, Miller M, Yang A, et al. Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40. Nature. 2017;552:368-373 pubmed publisher
    ..mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3...
  32. Wang X, Xu Q, Gao Y, Gao J, Li M, Yang W, et al. [Role of Rheb in Human Acute Myeloid Leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016;24:662-6 pubmed publisher
    To investigate the role of Rheb (mTOR activator) in AML development by measuring Rheb expression in bone marrow of adult AML patients and in AML cell line HL-60...
  33. Kim J, Kim E. Rag GTPase in amino acid signaling. Amino Acids. 2016;48:915-28 pubmed publisher
    ..acid stimulation, active Rag heterodimer (RagA/B(GTP)-RagC/D(GDP)) recruits mTORC1 to the lysosomal membrane where Rheb resides...
  34. Agarwal S, Bell C, Taylor S, Moran R. p53 Deletion or Hotspot Mutations Enhance mTORC1 Activity by Altering Lysosomal Dynamics of TSC2 and Rheb. Mol Cancer Res. 2016;14:66-77 pubmed publisher
    ..Subsequently, there was increased Rheb in the lysosomal compartment, and a higher mTOR association with Raptor...
  35. Caballero Garrido E, Pena Philippides J, Lordkipanidze T, Bragin D, Yang Y, Erhardt E, et al. In Vivo Inhibition of miR-155 Promotes Recovery after Experimental Mouse Stroke. J Neurosci. 2015;35:12446-64 pubmed publisher
    ..animals could be associated with stabilization of the TJ protein ZO-1 and mediated by the miR-155 target protein Rheb. MRI analysis showed significant (34%) reduction of infarct size in miR-155 inhibitor-injected animals at 21 d ..
  36. Guan Y, Zhang L, Li X, Zhang X, Liu S, Gao N, et al. Repression of Mammalian Target of Rapamycin Complex 1 Inhibits Intestinal Regeneration in Acute Inflammatory Bowel Disease Models. J Immunol. 2015;195:339-46 pubmed publisher
    ..Inhibition of mTORC1 activity by rapamycin treatment or haploinsufficiency of Rheb through genetic modification in mice impaired intestinal cell proliferation and induced cell apoptosis, leading to ..
  37. Lu Z, Shvartsman M, Lee A, Shao J, Murray M, Kladney R, et al. Mammalian target of rapamycin activator RHEB is frequently overexpressed in human carcinomas and is critical and sufficient for skin epithelial carcinogenesis. Cancer Res. 2010;70:3287-98 pubmed publisher
    Small GTPase Ras homologue enriched in brain (RHEB) binds and activates the key metabolic regulator mTORC1, which has an important role in cancer cells, but the role of RHEB in cancer pathogenesis has not been shown...
  38. Guo W, Han H, Wang Y, Zhang X, Liu S, Zhang G, et al. miR-200a regulates Rheb-mediated amelioration of insulin resistance after duodenal-jejunal bypass. Int J Obes (Lond). 2016;40:1222-32 pubmed publisher
    ..Ras homolog enriched in brain (Rheb) is reported to have an important role in insulin pathway, and some microRNAs (miRNAs) have been found to regulate ..
  39. Eom M, Han A, Yi S, Shin J, Cui Y, Park K. RHEB expression in fibroadenomas of the breast. Pathol Int. 2008;58:226-32 pubmed publisher
    ..The comparative expression of one of the identified genes, RAS homolog enriched in the brain (RHEB), was further explored using reverse transcriptase-polymerase chain reaction (RT-PCR)...
  40. He L, Ren Y, Zheng Q, Wang L, Lai Y, Guan S, et al. Fas-associated protein with death domain (FADD) regulates autophagy through promoting the expression of Ras homolog enriched in brain (Rheb) in human breast adenocarcinoma cells. Oncotarget. 2016;7:24572-84 pubmed publisher
    ..the FADD functions in breast cancer, we performed proteomics analysis by LC-MS/MS detection and found that Rheb-mTORC1 pathway was dysregulated in MCF-7 cells when FADD knockdown...
  41. Mohan N, Shen Y, Dokmanovic M, Endo Y, Hirsch D, Wu W. VPS34 regulates TSC1/TSC2 heterodimer to mediate RheB and mTORC1/S6K1 activation and cellular transformation. Oncotarget. 2016;7:52239-52254 pubmed publisher
    ..novel mechanisms by which VPS34 upregulates mTOR/S6K1 activity via downregulating TSC2 protein and activating RheB activity...
  42. Ode T, Podyma Inoue K, Terasawa K, Inokuchi J, Kobayashi T, Watabe T, et al. PDMP, a ceramide analogue, acts as an inhibitor of mTORC1 by inducing its translocation from lysosome to endoplasmic reticulum. Exp Cell Res. 2017;350:103-114 pubmed publisher
    ..the translocation of mTORC1 from late endosomes/lysosomes, leading to the dissociation of mTORC1 from its activator Rheb in MC3T3-E1 cells. Surprisingly, we found mTORC1 translocation to the ER upon PDMP treatment...
  43. Zhou L, Liu S, Han M, Feng S, Liang J, Li Z, et al. MicroRNA-185 induces potent autophagy via AKT signaling in hepatocellular carcinoma. Tumour Biol. 2017;39:1010428317694313 pubmed publisher
    ..Dual-luciferase reporter assays indicated that microRNA 185 suppressed the expression of target genes including RHEB, RICTOR, and AKT1 by directly interacting with their 3'-untranslated regions...
  44. De Cicco M, Kiss L, Dames S. NMR analysis of the backbone dynamics of the small GTPase Rheb and its interaction with the regulatory protein FKBP38. FEBS Lett. 2018;592:130-146 pubmed publisher
    Ras homolog enriched in brain (Rheb) is a small GTPase that regulates mammalian/mechanistic target of rapamycin complex 1 (mTORC1) and, thereby, cell growth and metabolism...
  45. Fansa E, Kösling S, Zent E, Wittinghofer A, Ismail S. PDE6?-mediated sorting of INPP5E into the cilium is determined by cargo-carrier affinity. Nat Commun. 2016;7:11366 pubmed publisher
    ..Here we show using the inositol polyphosphate 5'-phosphatase E (INPP5E) and the GTP-binding protein (Rheb) that cargo sorting depends on the affinity towards PDE6? and the specificity of cargo release...
  46. 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
    ..RagA GTPase recruitment of mTORC1 to the lysosomal outer surface, enabling activation of mTOR by the Ras homolog Rheb. Thereby, RagA alters mTORC1-driven growth in times of nutrient abundance or scarcity...
  47. Jacobs B, McNally R, Kim K, Blanco R, Privett R, You J, et al. Identification of mechanically regulated phosphorylation sites on tuberin (TSC2) that control mechanistic target of rapamycin (mTOR) signaling. J Biol Chem. 2017;292:6987-6997 pubmed publisher
    ..Recent studies have suggested that Ras homologue enriched in brain (Rheb), a direct activator of mTOR, and its inhibitor, the GTPase-activating protein tuberin (TSC2), may play a role in ..
  48. Wagner R, Martin K, Powell R, Rzucidlo E. Lovastatin induces VSMC differentiation through inhibition of Rheb and mTOR. Am J Physiol Cell Physiol. 2010;299:C119-27 pubmed publisher
    ..Lovastatin inhibition of mTORC1 was farnesylation dependent, suggesting the farnesylated G protein Rheb (Ras homologue enriched in brain), a known upstream activator of mTORC1...
  49. Campos T, Ziehe J, Palma M, Escobar D, Tapia J, Pincheira R, et al. Rheb promotes cancer cell survival through p27Kip1-dependent activation of autophagy. Mol Carcinog. 2016;55:220-9 pubmed publisher
    We previously found that the small GTPase Rheb regulates the cell-cycle inhibitor p27KIP1 (p27) in colon cancer cells by a mTORC1-independent mechanism. However, the biological function of the Rheb/p27 axis in cancer cells remains unknown...
  50. Hoxhaj G, Hughes Hallett J, Timson R, Ilagan E, Yuan M, Asara J, et al. The mTORC1 Signaling Network Senses Changes in Cellular Purine Nucleotide Levels. Cell Rep. 2017;21:1331-1346 pubmed publisher
    ..sensing by mTORC1 is dependent on the tuberous sclerosis complex (TSC) protein complex and its regulation of Rheb upstream of mTORC1, but independent of energy stress and AMP-activated protein kinase (AMPK)...
  51. Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, et al. Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. J Biol Chem. 2006;281:40242-51 pubmed
    ..1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse ..
  52. Siderovski D, Willard F. The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits. Int J Biol Sci. 2005;1:51-66 pubmed
    ..Discovery of these novel GAP, GDI, and GEF activities have helped to illuminate a new role for Galpha subunit GDP/GTP cycling required for microtubule force generation and mitotic spindle function in chromosomal segregation. ..
  53. Tatebe H, Shiozaki K. Evolutionary Conservation of the Components in the TOR Signaling Pathways. Biomolecules. 2017;7: pubmed publisher
    ..The studies have also identified two crucial regulators of mammalian TORC1 (mTORC1), Ras homolog enriched in brain (RHEB) and RAG GTPases...
  54. Altman M, Alshamrani A, Jia W, Nguyen H, Fambrough J, Tran S, et al. Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells. Cancer Lett. 2015;369:175-83 pubmed publisher
    ..b>Rheb is a small GTPase protein that shuttles between its GDP- and GTP-bound forms to activate mTOR...
  55. Groenewoud M, Zwartkruis F. Rheb and Rags come together at the lysosome to activate mTORC1. Biochem Soc Trans. 2013;41:951-5 pubmed publisher
    ..The activity of mTOR is under the control of various GTPases, of which Rheb and the Rags play a central role. The presence of amino acids is a strict requirement for mTORC1 activity...
  56. Shahani N, PRYOR W, Swarnkar S, Kholodilov N, Thinakaran G, Burke R, et al. Rheb GTPase regulates ?-secretase levels and amyloid ? generation. J Biol Chem. 2014;289:5799-808 pubmed publisher
    ..We demonstrate that Rheb GTPase (Ras homolog enriched in brain), which induces mammalian target of rapamycin (mTOR) activity, is a ..
  57. Yoshida S, Hong S, Suzuki T, Nada S, Mannan A, Wang J, et al. Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway. J Biol Chem. 2011;286:32651-60 pubmed publisher
    ..In this study, we show that the redox-sensitive regulation of mTORC1 occurs via Rheb but not the Rag small GTPase...
  58. Makovski V, Jacob Hirsch J, Gefen Dor C, Shai B, Ehrlich M, Rechavi G, et al. Analysis of gene expression array in TSC2-deficient AML cells reveals IRF7 as a pivotal factor in the Rheb/mTOR pathway. Cell Death Dis. 2014;5:e1557 pubmed publisher
    ..As they carry the same mutations, AML cell lines serve as a model for TSC and LAM. Rheb/mammalian target of rapamycin complex 1 (mTORC1) pathway is chronically activated in TSC-deficient cells, and this ..
  59. Shibutani S, Okazaki H, Iwata H. Dynamin-dependent amino acid endocytosis activates mechanistic target of rapamycin complex 1 (mTORC1). J Biol Chem. 2017;292:18052-18061 pubmed publisher
    ..the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb). However, how the extracellular amino acids reach the lysosomal lumen and activate mTORC1 remains unclear...
  60. Schewe D, Aguirre Ghiso J. ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo. Proc Natl Acad Sci U S A. 2008;105:10519-24 pubmed publisher
    ..Downstream, ATF6alpha induces survival through the up-regulation of Rheb and activation of mTOR signaling independent of Akt...
  61. Asrani K, Sood A, Torres A, Georgess D, Phatak P, Kaur H, et al. mTORC1 loss impairs epidermal adhesion via TGF-β/Rho kinase activation. J Clin Invest. 2017;127:4001-4017 pubmed publisher
    ..In mice with conditional epidermal loss of the mTORC1 components Rheb or Rptor, mTORC1 loss of function unexpectedly resulted in a profound skin barrier defect with epidermal abrasions, ..
  62. Hamada S, Hara K, Hamada T, Yasuda H, Moriyama H, Nakayama R, et al. Upregulation of the mammalian target of rapamycin complex 1 pathway by Ras homolog enriched in brain in pancreatic beta-cells leads to increased beta-cell mass and prevention of hyperglycemia. Diabetes. 2009;58:1321-32 pubmed publisher
    ..Studies in vitro have shown that the protein Ras homolog enriched in brain (Rheb) plays a key role as a positive upstream regulator of the mammalian target of rapamycin complex 1 (mTORC1) pathway ..
  63. Yu J, Henske E. Estrogen-induced activation of mammalian target of rapamycin is mediated via tuberin and the small GTPase Ras homologue enriched in brain. Cancer Res. 2006;66:9461-6 pubmed
    ..We hypothesized that tuberin and the small GTPase Ras homologue enriched in brain (Rheb), regulators of the mTOR pathway, mediate E(2)-induced activation of mTOR...
  64. Pryor W, Biagioli M, Shahani N, Swarnkar S, Huang W, Page D, et al. Huntingtin promotes mTORC1 signaling in the pathogenesis of Huntington's disease. Sci Signal. 2014;7:ra103 pubmed publisher
    ..experiments indicated that amino acids stimulated the interaction of Htt and the guanosine triphosphatase (GTPase) Rheb (a protein that stimulates mTOR activity), and that Htt forms a ternary complex with Rheb and mTOR...
  65. Inohara N, Ding L, Chen S, Nunez G. harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L). EMBO J. 1997;16:1686-94 pubmed
  66. Wätzlich D, Vetter I, Gotthardt K, Miertzschke M, Chen Y, Wittinghofer A, et al. The interplay between RPGR, PDE? and Arl2/3 regulate the ciliary targeting of farnesylated cargo. EMBO Rep. 2013;14:465-72 pubmed publisher
    ..On the basis of these results, we propose a model where RPGR is acting as a scaffold protein recruiting cargo-loaded PDE? and Arl3 to release lipidated cargo into cilia. ..
  67. Kim H, Ha S, Lee M, Huston E, Kim D, Jang S, et al. Cyclic AMP controls mTOR through regulation of the dynamic interaction between Rheb and phosphodiesterase 4D. Mol Cell Biol. 2010;30:5406-20 pubmed publisher
    ..Here, we identify cAMP phosphodiesterase 4D (PDE4D) as a binding partner of Rheb that acts as a cAMP-specific negative regulator of mTORC1...
  68. Uhlenbrock K, Weiwad M, Wetzker R, Fischer G, Wittinghofer A, Rubio I. Reassessment of the role of FKBP38 in the Rheb/mTORC1 pathway. FEBS Lett. 2009;583:965-70 pubmed publisher
    The small G-protein Rheb regulates cell growth via the mTORC1 complex by incompletely understood mechanisms...
  69. Thomas J, Zhang Y, Wei Y, Cho J, Morris L, Wang H, et al. Rab1A is an mTORC1 activator and a colorectal oncogene. Cancer Cell. 2014;26:754-69 pubmed publisher
    ..AA stimulates Rab1A GTP binding and interaction with mTORC1 and Rheb-mTORC1 interaction in the Golgi...
  70. Lv J, Yang L, Guo R, Shi Y, Zhang Z, Ye J. Ox-LDL-Induced MicroRNA-155 Promotes Autophagy in Human Endothelial Cells via Repressing the Rheb/ mTOR Pathway. Cell Physiol Biochem. 2017;43:1436-1448 pubmed publisher
    ..The effect of microRNA-155 on endothelial autophagy was observed along with the expression levels of Rheb, LC3B, Beclin1, and P62/SQSTM1 by western blotting (WB) and immunofluorescence through microRNA-155 overexpression ..
  71. Mazhab Jafari M, Marshall C, Stathopulos P, Kobashigawa Y, Stambolic V, Kay L, et al. Membrane-dependent modulation of the mTOR activator Rheb: NMR observations of a GTPase tethered to a lipid-bilayer nanodisc. J Am Chem Soc. 2013;135:3367-70 pubmed publisher
    Like most Ras superfamily proteins, the GTPase domain of Ras homologue enriched in brain (Rheb) is tethered to cellular membranes through a prenylated cysteine in a flexible C-terminal region; however, little is known about how Rheb or ..
  72. Nelson N, Clark G. Rheb may complex with RASSF1A to coordinate Hippo and TOR signaling. Oncotarget. 2016;7:33821-31 pubmed publisher
    ..The TOR pathway is regulated by activation of the Ras-related protein Rheb, which can bind mTOR...
  73. Lin J, Wang J, Greisinger A, Grossman H, Forman M, Dinney C, et al. Energy balance, the PI3K-AKT-mTOR pathway genes, and the risk of bladder cancer. Cancer Prev Res (Phila). 2010;3:505-17 pubmed publisher
  74. Hosokawa T, Kimura T, Nada S, Okuno T, Ito D, Kang S, et al. Lamtor1 Is Critically Required for CD4+ T Cell Proliferation and Regulatory T Cell Suppressive Function. J Immunol. 2017;199:2008-2019 pubmed publisher
    ..Previous studies using mice with conditional knockout of mTORC1 component proteins (i.e., mTOR, Raptor, and Rheb) gave conflicting results on the roles of mTORC1 in CD4+ T cells...
  75. Yu Y, Chang Y, Li S, Hu H, Huang Q, Ding J. Expression, purification, crystallization and preliminary structural characterization of the GTPase domain of human Rheb. Acta Crystallogr D Biol Crystallogr. 2004;60:1883-7 pubmed
    Ras homologue enriched in brain (Rheb) represents a unique group of small GTPases and shares moderate sequence identity with the Ras/Rap subfamily...