ライフサイエンスコーパス: Rheb

1 conserved (e.g. Rap) or not catalytic (e.g. Rheb).

2 abling activation of mTOR by the Ras homolog Rheb.

3 ator of the myogenic functions of raptor and Rheb.

4 ORC1) that was dependent on the small GTPase Rheb.

5 partment that contains the mTORC1 activator, Rheb.

6 osis of patients with cancers overexpressing RHEB.

7 t FTS inhibits mTOR at a level downstream of Rheb.

8 rin's ability to inactivate the small GTPase Rheb.

9 at is devoid of FKBP38 is still activated by Rheb.

10 lly increased by the addition of recombinant Rheb.

11 This binding induces the transactivation of Rheb.

12 or overexpression of mTOR-positive regulator Rheb.

13 that is devoid of raptor is not activated by Rheb.

14 compartment that also contains its activator Rheb.

15 ts GTPase-activating protein activity toward Rheb.

16 ssential for the oncogenic effects of mutant Rheb.

17 esting that PLD1 is a bona fide effector for Rheb.

18 action with its target small GTPase protein, Rheb.

19 mediated by 14-3-3 interaction with Tctp and Rheb.

20 3 proteins physically interact with Tctp and Rheb.

21 rface, where it interacts with its activator Rheb.

22 1 and mediated by the miR-155 target protein Rheb.

23 of its target Ras homolog enriched in brain (Rheb), a critical activator of mTOR signaling.

24 gested that Ras homologue enriched in brain (Rheb), a direct activator of mTOR, and its inhibitor, th

25 have no impact on the signals that regulate Rheb, a GTPase required for the activation of mTOR compl

26 We find that Rheb, a proximal activator of mTORC1, can produce rapid

27 Rheb, a Ras-related small GTPase, is a key upstream acti

28 lexes with the ubiquitin-E3-ligase Siah1 and Rheb, a small G protein that activates mTOR.

29 of the TOR (target of rapamycin) complex via Rheb, a small GTPase.

30 FKBP38, a recently proposed mediator of Rheb action, appears not to be involved in the Rheb-depe

31 In this study, we demonstrate that Rheb activates AMPK and reduces p27 levels in Tsc2-null

32 It has recently been shown that Rheb activates mTOR by binding to its endogenous inhibit

33 In summary, overexpression of Rheb activates mTOR signaling via a PI3K/PKB-independent

34 The overexpression of Rheb activates PLD1 in cells in the absence of mitogenic

35 RC1 signaling, which rather is determined by Rheb activation of mTOR catalytic activity, through mech

36 ind that PLD1, but not PLD2, is required for Rheb activation of the mTOR pathway, as demonstrated by

37 anism of TORC2 activation that is similar to Rheb activation of TOR complex 1.

38 stress, thereby reducing CM death induced by Rheb activation.

39 High Rheb activity in TSC mutant cells inhibits aggresome for

40 Consequently, when Rheb activity increases, cells become more resistant to

41 Moreover, Rheb activity toward mTORC1 requires farnesylation and i

42 We conclude that Rheb acts as a proto-oncogene in the appropriate genetic

43 Knockdown of FOG2, p110alpha, and RHEB ameliorated invasive and metastatic propensities of

44 -TBC1D7 complex (the TSC complex) to turn on Rheb, an essential activator of mTORC1.

45 nhibitory action of FKBP38 is antagonized by Rheb, an oncogenic small GTPase, which interacts with FK

46 nstitutively active form of the small GTPase Rheb, an upstream activator of mTor.

47 nduces survival through the up-regulation of Rheb and activation of mTOR signaling independent of Akt

48 otein 3 (BNIP3)-a negative regulator of both Rheb and Bcl2 prosurvival family members-as a key downst

49 ation of mTOR with positive regulators (i.e. Rheb and eIF3F) is consistent with an enhanced mRNA tran

50 xercise led to the dissociation of TSC2 from Rheb and increased in the co-localisation of mTOR and Rh

51 3 domain-containing protein, directly binds Rheb and inhibits the mTOR pathway.

52 In the presence of Rheb and insulin, PRAS40 release is abolished by Akt inh

53 skeletal muscle-specific knock-out mice for Rheb and iTSC2KO mice.

54 erodimer is a critical negative regulator of Rheb and mTOR activation.

55 equent study indicated an increased level of Rheb and mTOR expression in HCV-infected hepatocytes.

56 Rheb and mTORC1 may represent therapeutic targets to red

57 e lysosomal surface, where subpopulations of Rheb and mTORC1 reside.

58 exhibited deregulated cardiac activation of Rheb and mTORC1, particularly during ischemia.

59 x that acts as GTPase-activating protein for Rheb and negatively regulates the mammalian target of ra

60 nd Notch pathways, driven by the delivery of Rheb and Notch1 esRNA, in AML cells depleted of Rheb tha

61 However, how the TSC/Rheb and PLD pathways interact or integrate in the rapam

62 molecular weight GTP-binding proteins of the Rheb and Rag families are key regulators of the mTORC1 c

63 that C. elegans expresses orthologs for the Rheb and RalA/B GTPases and for RalGAPalpha/beta, but no

64 wnstream of the farnesylated small G protein Rheb and synergistically enhanced etoposide-induced anti

65 ggest that FKBP38 is a bona fide effector of Rheb and that the ability to interact with FKBP38 is imp

66 atively regulates the activity of the GTPase Rheb and thereby inhibits mammalian target of rapamycin

67 sults not only establish a critical role for Rheb and TSC2 in the mechanical activation of mTOR signa

68 ally targets a farnesylated protein, such as Rheb, and a geranylgeranylated protein, such as Rho, bot

69 , but FTS could be a promising treatment for Rheb- and mTOR-dependent cancers.

70 In contrast, mTORC1 regulators Raptor and Rheb are dispensable for NKT17 differentiation, despite

71 The hypertrophic effects of Rheb are driven through a rapamycin-sensitive (RS) mecha

72 Altogether, our study defines Rheb as a novel physiological regulator of BACE1 levels

73 ity to interact with FKBP38 is important for Rheb as an activator of mTOR.

74 We report the mTOR activator gene RHEB as an ID gene that is associated with megalencephal

75 ORC1 through the combined effects of TSC and RHEB as part of a multiprotein complex localized on lyso

76 recruitment of mTORC1 and the TSC complex to Rheb at the lysosomal surface serve to integrate diverse

77 f BACE1 levels and Abeta generation, and the Rheb-BACE1 circuitry may have a role in brain biology an

78 The activation of mTORC1 is specific to Rheb, because other G-proteins such as KRas, RalA/B, and

79 Finally, Rheb binds and activates PLD1 in vitro in a GTP-dependen

80 RHEB binds to mTOR distally from the kinase active site,

81 mall GTPase Ras homologue enriched in brain (RHEB) binds and activates the key metabolic regulator mT

82 ox-sensitive regulation of mTORC1 occurs via Rheb but not the Rag small GTPase.

83 ruitment of Ras homologue enriched in brain (Rheb) but not mammalian target of rapamycin (mTOR) to en

84 ology domain responsible for inactivation of Rheb, but functions of other protein domains remain elus

85 TORC1 is controlled by the small GTPase Rheb, but little is known about TORC2 regulators.

86 In Pten-deficient tumor cells, inhibition of Rheb by FTI is responsible for the drug's anti-tumor eff

87 , arginine relieves allosteric inhibition of Rheb by TSC.

88 tively active Ras-homolog enriched in brain (Rheb(CA)) into subventricular zone NPCs increased mTOR a

89 At >19 dpe, newborn Rheb(CA)-expressing neurons displayed altered distributi

90 The activation of mTORC1 by Rheb can be faithfully reproduced in vitro by using mTOR

91 g a constitutively active form of the GTPase Rheb (caRheb) in adult neurons after a complete SCI in r

92 Rheb causes mTORC1-dependent effects on apoptosis, senes

93 By interfering with TSC-Rheb complex, arginine relieves allosteric inhibition of

94 proteins and their target, the small GTPase Rheb, constitute a key regulatory pathway upstream of mT

95 Furthermore, Tsc2 deficiency and hyperactive Rheb constitutively activated mTOR and inhibited ephrin-

96 study, we investigated the possibility that Rheb controls apoptosis by regulating the interaction of

97 Taken together, our data suggest that Rheb controls proliferation of TSC2-deficient cells by a

98 es are consistently dephosphorylated in both Rheb-deficient CD4(+) T cells and T cells treated with r

99 By analyzing activated murine wild-type and Rheb-deficient CD4(+) T cells, as well as murine CD4(+)

100 However, these RHEB-deficient memory-like T cells failed to generate re

101 Rheb-deficient T cells failed to generate T(H)1 and T(H)

102 eb action, appears not to be involved in the Rheb-dependent activation of mTORC1 in vitro, because th

103 SC complex associates with the lysosome in a Rheb-dependent manner, and its dissociation in response

104 biallelic TSC2 mutations exhibited TSC2- and Rheb-dependent Notch activation.

105 Importantly, we found that the Rheb-dependent release of Bcl-X(L) from FKBP38 facilitat

106 Furthermore, increased p27 levels following Rheb depletion correlated with reduced Cdk2 activity and

107 forms abolishes the binding between Tctp and Rheb, disrupting organ development.

108 Active Rheb disrupts the interaction between dynein and misfold

109 On the other hand, the addition of Rheb does not activate mTORC2 immunoprecipitated from ma

110 Rheb does not induce autophosphorylation of mTOR.

111 mber and organ size, which mimics Drosophila Rheb (dRheb) mutant phenotypes.

112 Moreover, Rheb-driven mTOR S2481 autophosphorylation and S6K1 phos

113 f Tsc1 and overexpression of the Ras homolog Rheb each resulted in duplication of the bristle and soc

114 Expression of a constitutively active Rheb enhanced mTOR activity and increased the fiber size

115 xpected, the knockdown of raptor, as well as Rheb, enhances differentiation.

116 omal delivery of exosomal shuttle Notch1 and Rheb esRNA and component of gamma-secretase complex pres

117 This leads to Rheb expression and potentiates mTOR signaling to drive

118 Furthermore, increased Rheb expression likely contributes to mTOR activation in

119 nction in epithelial malignancy, we targeted Rheb expression to murine basal keratinocytes of transge

120 Our findings offer direct evidence that RHEB facilitates multistage carcinogenesis through induc

121 CD4(+) T cells lacking the mTORC1 activator Rheb fail to secrete IFN-gamma under Th1 polarizing cond

122 ue to loss of RAS homolog enriched in brain (RHEB) failed to differentiate into effector cells but re

123 ) mutant prevented small GTP-binding protein Rheb from enhancing the phosphorylation of S6 kinase (S6

124 t inhibitors of Icmt and Rce1 will not block Rheb function, but FTS could be a promising treatment fo

125 nd independent of Rag and Ragulator, but not Rheb, function.

126 Rheb G-protein plays critical roles in the TSC/Rheb/mTOR

127 Rheb G63A stimulated phosphorylation of the mTORC1 subst

128 iation of TSC1 and TSC2 leading to decreased Rheb-GAP activity, without effects on the localization o

129 fic cellular growth conditions and possesses Rheb-GAP activity.

130 Substitution of Rheb Gly-63 with alanine impaired both intrinsic and TSC

131 th cysteine oxidants significantly increases Rheb GTP levels.

132 cells where the perinuclear localization of Rheb-GTP and mTOR coincided with the perinuclear assembl

133 colocalization of mTORC1 with its activator Rheb-GTP in a perinuclear region, thereby inducing 4E-BP

134 y increasing PI3K/Akt-mediated activation of Rheb-GTP via TSC2 suppression.

135 d manner and promote mTORC1 interaction with Rheb-GTP, the immediate activator.

136 anner through the colocalization of mTOR and Rheb-GTP, which occurs in association with the formation

137 no acid-dependent steps couple Rag-mTORC1 to Rheb-GTP.

138 We demonstrate that Rheb GTPase (Ras homolog enriched in brain), which induc

139 In summary, the Rheb GTPase is an oncogenic activity upstream of mTORC1

140 We report here that Rheb GTPase, the upstream activator of the mTOR complex

141 ts mTOR kinase signaling by inactivating the Rheb GTPase.

142 ionally controlled tumour protein (Tctp) and Rheb GTPase.

143 ling components, including raptor, S6K1, and Rheb, had been suggested in muscle maintenance, growth,

144 olecules required for positive regulation of Rheb have not been identified.

145 mitogenic stimulation, and the knockdown of Rheb impairs serum stimulation of PLD activation.

146 raction of FKBP38 with Bcl-2 is regulated by Rheb in a GTP-dependent manner.

147 ortant role in cancer cells, but the role of RHEB in cancer pathogenesis has not been shown.

148 This study reveals a function of Rheb in controlling misfolded protein metabolism by modu

149 The TSC1/2 proteins inhibit Rheb in mammals, and Tsc1/Tsc2 inhibit Rhb1 in S. pombe.

150 ured cells, the interaction is controlled by Rheb in response to changes in amino acid and growth fac

151 estigated the functions of raptor, S6K1, and Rheb in the differentiation of C2C12 mouse myoblasts.

152 nversion prevents mTOR from interacting with Rheb in the late endosomal compartment.

153 The role of Rheb in the regulation of cell survival during ED has no

154 ab5CA, whereas hyperactivation of endogenous Rheb in TSC2-/- MEFs did not.

155 Functional testing of mutant RHEB in vertebrate animal models indicates pathway hyper

156 Expression of dMyc, but not of CycD/cdk4 or Rheb, in the FB diminishes the ability to retain Drosoph

157 expression of RAS homolog enriched in brain (RHEB) increased mTORC1 signaling, promoted a switch to a

158 te cell growth and glioma formation in a TSC/Rheb-independent fashion.

159 Collectively, these findings establish TSC/Rheb-independent mechanisms for mTOR-dependent glial cel

160 d Ras homolog enriched in brain-independent (RHEB-independent) mTORC1 activation.

161 Constitutively active mutants of Rheb induce oncogenic transformation in cell culture.

162 ith the binding of 4EBP1 to mTORC1, inhibits Rheb-induced activation of mTORC1.

163 or Rheb localization, but is dispensable for Rheb-induced activation of the mTOR substrate p70 S6 kin

164 ibits cell growth, S6K1 phosphorylation, and rheb-induced activation of the mTORC1 pathway, and in vi

165 Rheb-induced transformation is also dependent on a C-ter

166 Rheb-induced tumor persistence and neoplastic molecular

167 These results suggest that Rheb induces alteration in the binding of 4E-BP1 with mT

168 Rheb inhibition causes mTORC1 inhibition, because forced

169 Rheb inhibits autophagy mostly through Atg7 depletion.

170 s in myogenesis, overexpression of raptor or Rheb inhibits C2C12 differentiation.

171 n 3T3-L1 adipocytes by ectopic expression of Rheb inhibits expression of ATGL and HSL at the level of

172 Moreover, GTP-bound Rheb interacts with BACE1 and degrades it through protea

173 In this study, we show that Rheb interacts with FKBP38 through a section within its

174 utively active form of the mTORC1 regulator, Rheb, into HD mouse brain, alleviates mitochondrial dysf

175 skeletal muscle-specific knock-out mice for Rheb (iRhebKO) and TSC2 (iTSC2KO) and mechanically stimu

176 Rheb is a GTP-binding protein that promotes cell surviva

177 nvolves regulation of AMPK and p27, and that Rheb is a potential target for TSC/LAM therapy.

178 Rheb is a Ras family GTPase, which binds to and activate

179 The Ras-like small GTPase Rheb is an upstream activator of the mammalian target of

180 In fission yeast, Rheb is encoded by the rhb1 gene.

181 Notably, RHEB is highly expressed in some human lymphomas, result

182 Rheb is inactivated during cardiomyocyte (CM) glucose de

183 motes BACE1 accumulation, and this effect by Rheb is independent of its mTOR signaling.

184 ly, this previously unrecognized function of Rheb is independent of TOR complex 1.

185 Indeed, we found that Rheb is required for EGF-dependent mTOR activation in sp

186 We also find that the effector domain of Rheb is required for the mTORC1 activation.

187 Rheb is targeted to endomembranes via its C-terminal CAA

188 e domain of Ras homologue enriched in brain (Rheb) is tethered to cellular membranes through a prenyl

189 ompanied by inhibition of autophagy, whereas Rheb knockdown increased autophagy and CM survival.

190 hanced differentiation elicited by raptor or Rheb knockdown is accompanied by increased Akt activatio

191 ent in differentiation elicited by raptor or Rheb knockdown, suggesting that IRS1 is a critical media

192 Siah1 degrades Rheb leading to reduced mTOR signaling, while ketamine,

193 Finally, we demonstrate that Rheb levels are down-regulated in the AD brain, which is

194 from AML cells with the constitutively high Rheb levels.

195 ther farnesylthiosalicylic acid (FTS) blocks Rheb localization and function.

196 hat Icmt and Rce1 processing is required for Rheb localization, but is dispensable for Rheb-induced a

197 in of chromosome 7q36.1-q36.3 containing the RHEB locus, an overexpression of RHEB mRNA in several di

198 Rheb markedly sensitized transgenic epidermis to squamou

199 riven NSC proliferation results from tuberin/Rheb-mediated mammalian target of rapamycin (mTOR) hyper

200 taining the RHEB locus, an overexpression of RHEB mRNA in several different carcinoma histotypes, and

201 fering RNA (siRNA)-induced downregulation of Rheb, mTOR, or raptor, but also by siRNA for rictor.

202 argeting survival signaling by the ATF6alpha-Rheb-mTOR pathway in dormant tumor cells may favor the e

203 3-kinase (PI3K)-dependent activation of the Rheb-mTOR pathway triggers the simultaneous local synthe

204 Our results indicate that TSC2-Rheb-mTOR signaling cooperates with the ephrin-Eph recep

205 -Tsc2 loss activated RalA/B independently of Rheb-mTOR signaling.

206 in brain-mammalian target of rapamycin (TSC-Rheb-mTOR) pathway is known to play a central role in mo

207 In conclusion, the Rheb-mTOR/raptor pathway negatively regulates myogenic d

208 loped based on NF1's central role in the RAS/RHEB/mTOR signal transduction pathway.

209 eb G-protein plays critical roles in the TSC/Rheb/mTOR signaling pathway by activating mTORC1.

210 ograde axon degeneration is regulated by Akt/Rheb/mTor signaling pathways.

211 GTP binding and interaction with mTORC1 and Rheb-mTORC1 interaction in the Golgi.

212 demonstrate that the interplay between Tsc1-Rheb-mTORC1 signaling and Myc-dependent bioenergetic and

213 and the 3.4 angstrom structure of activated RHEB-mTORC1.

214 de the activation of a previously unreported Rheb-Notch-Rheb regulatory loop, in which the cyclic bin

215 expressing either constitutively active (ca) Rheb or a caRagB.caRagC complex, and coexpression of the

216 l region; however, little is known about how Rheb or other GTPases interact with the membrane or how

217 onal epidermal loss of the mTORC1 components Rheb or Rptor, mTORC1 loss of function unexpectedly resu

218 Rheb overexpression depletes BACE1 protein levels and re

219 Furthermore, Rheb overexpression in 293E activated mTORC1 signaling c

220 Third, conditional Tsc1 inactivation or Rheb overexpression in glial progenitors of Nf1(+/-) mic

221 , because forced activation of Rheb, through Rheb overexpression in vitro and through inducible cardi

222 vitro and through inducible cardiac-specific Rheb overexpression in vivo, restored mTORC1 activity.

223 Rheb overexpression increases phosphorylation on raptor

224 We demonstrate that Rheb overexpression promotes hyperplasia and a low-grade

225 that Pten haploinsufficiency cooperates with Rheb overexpression to markedly promote prostate tumorig

226 1 or Pten inactivation, but not Tsc1 loss or Rheb overexpression, increases astrocyte cell growth in

227 f raptor Ser(863) via the canonical PI3K/TSC/Rheb pathway in a rapamycin-sensitive manner.

228 Consistent with a TSC-Rheb-PLD signaling cascade, AMPK and PI3K, both establis

229 increased in the co-localisation of mTOR and Rheb post exercise in both FED and CON.

230 The identified NRE2 and NRE3 on the Rheb promoter are important to Notch-dependent promoter

231 the Notch-responsive elements (NREs) on the Rheb promoter is a key event.

232 on, whereas the RNAi knockdown of endogenous Rheb promotes BACE1 accumulation, and this effect by Rhe

233 Inactivation of Rheb protects CMs during ED through activation of autoph

234 altered association of mTOR with RagB/RagC, Rheb, raptor, and PRAS40.

235 bromin) glial growth regulation requires TSC/Rheb (Ras homolog enriched in brain) control of mTOR fun

236 ively active variant of an mTORC1 activator, Rheb (Ras homolog enriched in brain), could not prevent

237 llular killing of P. aeruginosa by targeting Rheb (Ras homolog enriched in brain).

238 mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by

239 Activation of the TSC pathway is mediated by Rheb (Ras homologue enriched in brain), a Ras superfamil

240 he colocalization of mTOR and its activator, Rheb (Ras homology enriched in brain)-GTP, to a perinucl

241 Rheb (Ras-homolog enriched in brain) is a component of t

242 gether, these data indicate that the TSC and Rheb regulate Notch-dependent cell-fate decision in Dros

243 We show that Rheb regulates mTOR through FKBP38, a member of the FK50

244 vation of a previously unreported Rheb-Notch-Rheb regulatory loop, in which the cyclic binding of Not

245 provide biochemical evidence that they mimic RHEB relieving auto-inhibition.

246 h that a farnesylation-independent mutant of Rheb renders these tumors resistant to FTI therapy.

247 The addition of Rheb results in a significant increase of binding of the

248 ta also suggest that while overexpression of rheb results in aberrant synaptic overgrowth, the overgr

249 sfection with Ras homolog enriched in brain (Rheb) revealed that a PKB-independent activation of mamm

250 Down-regulation of ATF6alpha or Rheb reverted dormant tumor cell resistance to rapamycin

251 strocyte hyperproliferation is unaffected by Rheb shRNA silencing.

252 ation inhibitor beta, which likely regulates RHEB shuttling between GDP-bound and GTP-bound forms.

253 that 4,4'-biphenol (5) selectively inhibits Rheb signaling and induces cell death suggesting that th

254 nch, independent of the conventional Akt/TSC/Rheb signaling axis.

255 cells leading to the activation of Notch and Rheb signaling in the recipient cells.

256 Here we focus on mTORC1 and show that TSC/Rheb signaling promotes mTOR S1261 phosphorylation in an

257 renylation processing steps are required for Rheb signaling through mTOR is not known.

258 via PLCgamma/DAG/PKC signaling, not via Akt/Rheb signaling.

259 that, in skeletal muscle, overexpression of Rheb stimulates a PI3K/PKB-independent activation of mTO

260 nsformation induced by constitutively active Rheb, suggesting that TOR activity is essential for the

261 To identify the regions of the Rheb surface most critical for signaling to TOR complex

262 ging 65 residues distributed over the entire Rheb surface.

263 f the minimal impact of guanyl nucleotide on Rheb switch 2 configuration.

264 We used NMR methods to characterize Rheb tethered to nanodiscs, monodisperse protein-encapsu

265 ling, while ketamine, conversely, stabilizes Rheb that enhances mTOR signaling.

266 s of membrane-dependent signal regulation by Rheb that shed light on previously unexplained in vivo p

267 b and Notch1 esRNA, in AML cells depleted of Rheb that were treated with the exosomes purified from A

268 tase E (INPP5E) and the GTP-binding protein (Rheb) that cargo sorting depends on the affinity towards

269 ase-activating protein (GAP) activity toward Rheb, this complex inhibits the mechanistic target of ra

270 RC1 inhibition, because forced activation of Rheb, through Rheb overexpression in vitro and through i

271 through the Rag complex and insulin through Rheb to achieve coordinate activation of mTORC1.

272 Using overexpression of Rheb to activate TORC1 and Rictor plus Sin1 to augment T

273 Notch cooperates with Rheb to block cell differentiation via similar mechanism

274 Further, Tsc1 signaled through Rheb to down-regulate mTORC1 for proper DC development,

275 ostinjury to express a constitutively active Rheb to enhance their intrinsic growth potential, transp

276 ynergistic genetic interaction with Tctp and Rheb to impair tissue growth.

277 We find that the ability for Rheb to interact with FKBP38 correlates with its activit

278 ofluorescence localizes wild-type and mutant Rheb to vesicular structures in the cytoplasm, overlappi

279 nd the GTPase Ras homolog enriched in brain (Rheb) to induce regrowth of axons after they have been d

280 by their ability, in comparison to wild type Rheb, to restore the phosphorylation of S6K1(Thr389) whe

281 uirement for amino acid sensing via Slimfast/Rheb/TOR complex 1.

282 By rapidly infiltrating tumors, RHEB-transduced T cells significantly reduced the emerge

283 sequencing efforts have identified recurrent Rheb Tyr35Asn mutations in kidney and endometrial carcin

284 rexpression of the small GTP-binding protein RheB under nutrient starvation.

285 After farnesylation, Rheb undergoes two additional CAAX-signaled processing s

286 inoma histotypes, and an association between RHEB upregulation and poor prognosis in breast and head

287 PTOR, together with their upstream activator Rheb, was sufficient to provide TORC1 activity and stimu

288 ity to interact directly with K-Ras and that Rheb weakly binds to bisphenol A (10) and 4,4'-biphenol

289 Overexpression of Rheb, which activates mTOR independently of mTOR localiz

290 ignaling, but does not inhibit the effect of Rheb, which directly binds and activates mTORC1.

291 ignaling, but does not inhibit the effect of Rheb, which directly binds to and activates mTORC1.

292 mTORC1 is regulated by the small GTPase Rheb, which in turn is regulated by the GTPase-activatin

293 PLD is a downstream target of the GTPase Rheb, which is turned off in response to AMPK via the tu

294 The interaction of Rheb with FKBP38 is controlled by its guanine nucleotide

295 Finally, we demonstrate that Rheb-WT can bind AMPK to facilitate AMPK activation, whe

296 Here we show that Rheb-Y35N causes not only constitutive mTORC1 activation

297 AMPK to facilitate AMPK activation, whereas Rheb-Y35N competitively binds AMPK, impairing AMPK phosp

298 Furthermore, Rheb-Y35N inhibits AMPKalpha activation in response to n

299 In summary, our findings indicate that Rheb-Y35N is a dominantly active tumor driver that activ

300 Rheb-Y35N transforms NIH3T3 cells, resulting in aggressi