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RHEB activates MTOR. 448 / 458
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"In addition, from a methodologic perspective, Rheb CA expression rapidly (6-8 hours) activates the mTOR pathway as compared to other experimental strategies such as conditional transgenic mice, small hairpin RNA (shRNA), or CRISPR and Cas9 vectors because the timing of mTORC1 activation depends on the half-life of the KD/KO protein of interest."
31625153
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"Indeed, we have shown, as a proof of principle, that knocking down TSC2 or overexpressing RHEB enhances mTOR activity in KO cells."
28130275
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"Rheb activation of mTOR is more dependent on farnesylation than on postprenylation CAAX processing."
19838215
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"This explains why overexpressed Rheb activates mTOR in the absence of amino acids; presumably the Rheb-mTOR interaction is driven by mass action in this case, and no longer requires the amino acid stimulated movement of mTOR to late endosomes."
20053679
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"Rheb has been shown to exclusively activate the mTOR pathway without affecting other signaling pathways."
27264357
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"Akt mediated phosphorylation can downregulate tuberin 's GTPase activating potential toward Rheb, which modulates mTOR complex 1 through FKBP38 by directly binding to mTOR [XREF_BIBR]."
26244501
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"Full-length TSC2 protein interacts with TSC1 to inhibit the activation of mTOR by Rheb."
24318044
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"When free of TSC1/2, RHEB activates mTOR within a rapamycin sensitive protein complex called mTORC1."
22483044
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"Previous studies have shown that the small GTPase Rheb increases mTOR activity by sequestering the mTOR inhibitor FKBP-38 (Bai et al., 2007; Codeluppi et al., 2009)."
20538043
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"Amino acids on the other hand signal to mTORC1 through the Rag family of GTPases, by mediating the activation of mTOR by RHEB at the lysosome [XREF_BIBR, XREF_BIBR]."
26255626
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"As mTOR is an inhibitor of autophagy xref , and RHEB activates mTOR, it may not be surprising that FTIs can induce autophagy, possibly by blocking RHEB function xref ."
22020205
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"Another example of a non-canonical ATF6-regulated gene product is the small GTPase Ras homolog enriched in brain (Rheb), which, when induced by ATF6α in the heart, activates mammalian target of rapamycin complex 1 (mTORC1) and thus drives protein synthesis and hypertrophic cardiac myocyte growth [66]."
32046286
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"In contrast, although Rce and Icmt were required for proper Rheb localization, neither of the post-prenyl processing steps was required for Rheb-induced mTOR activation."
19838215
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"The function of Rheb is to bind to and activate mTOR and thus, it is essential for coupling all upstream signals to this pathway."
26319900
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"With TSC inhibited by AKT, the active GTP-bound RHEB can activate mTOR on the lysosome [ xref , xref , xref ]."
| PMC
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"Our laboratory examined the effects of forced overexpression of the known mTOR activator Rheb2 that has been shown to be preferentially expressed in HSC populations [XREF_BIBR]."
21411351
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"By blocking NMDAR activation, ketamine stabilizes Rheb, which in turn increases mTOR activation (Harraz et al., 2016)."
34566558
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"Rheb is the upstream activator of mTOR."
26410619
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"Renal mTOR activation in poorly controlled diabetes may result from a combination of AKT inhibition of tuberous sclerosis complex 2, hyperglycemia induced AMPK inhibition, and increased glucose uptake through glucose transporter 1, in which the resulting increased glycolysis and activation of GAPDH can lead directly to Rheb activation of mTOR by reducing Rheb binding to GAPDH."
24705402
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"Protein mTOR complex 1 (mTORC1) functions as a major sensor for the nutrient, energy, and redox state of a cell and is activated by ras homolog enriched in brain (RHEB1), a GTP binding protein."
28891034
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"Activated Rheb binds and activates the mTOR kinase, constitutively driving the TOR pathway [ xref , xref ]."
27034171
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"Surprisingly, TSC2 GAP domain also bound nucleotide-free Rheb as well as GMPPNP charged Rheb.The ability of Rheb to bind directly to mTOR impelled us to examine whether Rheb directly regulates mTOR ki[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15854902
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"Rheb modulates the mTOR complex and controls protein synthesis via the phosphorylation of 4E-BP1 and S6."
30072674
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"This mechanism results in spatial separation and thus dissociation of TSC2 from lysosome and reliefs the inhibitory effect of TSC2 on the mTOR activator Rheb, leading to activation of mTORC1-S6K1 signaling."
29472548
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"To investigate whether the DDIT4 and mTOR signaling pathway is involved in regulating the proliferation of RMCs treated with 1,25 (OH) 2 D 3, we examined the expression of VDR, DDIT4, TSC1 and TSC2, the mTOR mediator Rheb, mTOR, and its downstream proteins 4E-BP1 and p70S6K by Western blot."
29416624
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"Hamartin and tuberin, the protein products of TSC1 and TSC2 , respectively, form a functional heterodimer that negatively regulates cell growth via tuberin's GTPase Activating Protein activity toward the small GTPase Rheb, which in turn activates the mechanistic target of rapamycin complex 1 (mTORC1)."
25565629
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"Significantly, Rheb is fully active when constitutively targeted to the Golgi apparatus and its association with this organelle 8 h after transfection coincides with the activation of p70S6K, suggesti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16631613
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"In this study we reveal that Rheb enhances mTOR mediated signaling toward S6K1 and 4E-BP1."
12906785
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"The differentially expressed protein Rheb, a homolog of Ras GTPase, participates in the PI3K/AKT/mTOR signaling pathway and upregulates Rheb activated mTOR activity."
34177563
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"To further determine whetherENDOG mediated autophagy promotion is mTOR dependent, we used a constitutively active form of RHEB (RHEB Q64L) to continuously activate mTOR 19."
33473107
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"MTOR activation by Rheb overexpression decreases the CD133+ subpopulations."
22145042
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"As mTOR is an inhibitor of autophagy 121, and RHEB activates mTOR, it may not be surprising that FTIs can induce autophagy, possibly by blocking RHEB function 122."
22020205
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"Previous work showed Rheb can signal both mTOR dependent and -independent pathways, and we found that Rheb can signal eIF2alpha, a target implicated in AD."
27960107
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"The proteins encoded by TSC1 (hamartin) and TSC2 (tuberin) normally form a complex that regulates the mTORC1 signaling pathway directly through inhibition of the mTOR activator rheb (ras homologue expressed in brain) [XREF_BIBR]."
28232951
eidos
"Amino acids promote the recruitment of mTOR to the lysosomal surface , where mTOR is activated by RHEB ."
| PMC
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"Rheb-GTP activates mTOR by phosphorylating mTOR on Ser 2448 xref ."
22900043
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"Interestingly, the late-phase decrease in mTOR activation we observed coincided with decreased expression of the upstream mTOR activator Rheb, suggesting a possible negative-feedback mechanism (XREF_FIG)."
25340958
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"Most upstream they target TSC1, a negative regulator of mTOR signaling that in its absence allows Rheb to activate mTOR."
31232238
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"RHEB may activate mTOR either by directly binding to it xref or by binding to the mTOR antagonist FKBP38 (also known as FKBP8) xref ."
22020205
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"At the lysosome surface, the small GTPase Rheb activates mTOR, and active mTORC1 promotes anabolic processes and inhibits autophagy [ xref ]."
28656016
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"Tsc2 exerts its tumor suppressor function by acting as a GTPase activating protein for the mTOR activator Rheb [21]."
32327294
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"This may be due to reduction in AMP-activated protein kinase signaling [ xref ] or due to the decreased interaction of glyceraldehyde 3-phosphate dehydrogenase and Rheb [ xref ], each of which would promote mTOR activation (specifically, the mTORC1 complex) by the small GTPase Rheb ( xref )."
20224802
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"MTOR is activated by the GTPase Rheb which in turn is controlled by the TSC1 and TSC2 complex."
20616901
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"Studies showed the underlying mechanism for physiological regulating BACE1 stability and activity in its GTP-bound state was Rheb GTPase, which induced mammalian target of rapamycin (mTOR) activity."
31213978
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"When free of TSC1/2, RHEB activates mTOR within a rapamycin-sensitive protein complex called mTORC1."
22483044
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"To confirm the regulation role of mTOR in G9a inhibition induced autophagy, we next overexpressed Rheb, which intensively activates mTOR in TCC T24 and UMUC-3 [XREF_BIBR]."
26397365
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"Rheb is a direct activator of mTOR and the only known downstream target of Rheb is mTOR."
27264357
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"Rheb positively regulates mTOR signaling and co-immunoprecipitate with mTOR [XREF_BIBR]."
19285959
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"We mapped the mutations onto the crystal structures of both the apo and RHEB-activated mTOR proteins (Figure 2A)."
34538873
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"Rheb can activate mTOR signaling pathway and participate in genesis and development of multiple cancers."
23628014
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"Ras and Rheb also enhances mTOR and raptor signaling, stimulating p70S6 kinase- and eIF4E (eukaryotic translation initiation factor 4E)-regulated cell growth, autophagy, metabolism, ribosome biogenesis and translation [XREF_BIBR]."
22172248
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"We determined that Icmt and Rce1 processing is required for Rheb localization, but is dispensable for Rheb-induced activation of the mTOR substrate p70 S6 kinase (S6K)."
19838215
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"Growth factor deprivation leads to inactivation of Akt protein kinase, activation of tuberous sclerosis 1/2 (TSC1/2), and inactivation of Rheb, thus attenuated Rheb activation of mTOR XREF_BIBR."
25618581
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"Rheb activates mTOR to suppress autophagy and promote transformation [XREF_BIBR]."
27034171
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"Rheb has been shown to bind directly to the amino-terminal lobe of the mammalian TOR (mTOR) catalytic domain and activate mTOR in a GTP dependent manner."
21035549
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"Land and Tee (2007) have shown that Rheb-specific activation of mTOR enhanced the transcriptional activity of HIF-1α during hypoxia."
31632293
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"Notably, several ASD risk genes are present in mTOR signaling, including IGF1, MTOR, PIK3R2, PTEN, RHEB, TSC1, and TSC2."
34744804
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"Recent studies have shown that an mTOR containing complex, mTORC1, is targeted to lysosomes in the presence of amino acids and activated by Rheb GTPase resident in that compartment."
21063721
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"These cytotoxic effects have been attributed to FTI induced inhibition of prosurvival signaling by Akt, the Rheb target mTOR, or mitogen activated protein (MAP) kinases."
19707379
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"Nitrosylated GAPDH complexes with the ubiquitin-E3-ligase Siah1 and Rheb, a small G protein that activates mTOR."
26782056
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"TSC1/2 negatively regulates Rheb, which directly activates mTOR."
23392671
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"Tuberin is a GAP for Rheb, which activates mTOR in the guanosine triphosphate–bound state."
33773987
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"One important mode of action of AMPK is through the inhibition of mTORC1, which can be achieved through various mechanisms [19] such as a direct phosphorylation of the tumour suppressor TSC2 to negati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23612073
sparser
"Taken together, these data suggest that Rheb activation of mTOR is more dependent on farnesylation than on Rce1- and Icmt-catalyzed modifications."
19838215
sparser
"MTOR can be activated by RHEB either on the surface of the peroxisome [ xref ]–in response to reactive oxygen species (ROS)–or on the surface the lysosome [ xref ]–in response to amino acids."
29570707
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"In addition, we found that activation of mTOR by Rheb2 or a constitutively active RagB mutant (RagB GTP), like overexpression of p62 itself, enhances the soft agar growth of A498 cells (XREF_SUPPLEMENTARY)."
24332042
sparser
"Tuberin is a GAP for Rheb, which activates mTOR in the guanosine triphosphate–bound state."
33773987
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"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."
28319048
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"When bound to GTP Rheb activates mTOR and when bound to GDP it inhibits mTOR."
19796712
sparser
"Amino acids on the other hand signal to mTORC1 through the Rag family of GTPases, by mediating the activation of mTOR by RHEB at the lysosome [ xref , xref ]."
26255626
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"In this study, we demonstrate that the overexpression of Rheb induces mTOR signaling through a PI3K and PKB independent mechanism and that this event is sufficient to induce a robust and cell autonomous hypertrophic response."
20668162
sparser
"Akt is known to activate mTOR signaling through the phosphorylation of TSC2, thus allowing the downstream activation of mTOR by Rheb GTPase and the recruitment of Raptor by means of the TOS motif ."
23291002
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"Next, we introduced the dominant negative D60K [23] and the constitutively-active Q64L [24] mutants of Rheb in HeLa cells to further demonstrate the involvement of Rheb in S1P induced mTOR activation."
19000755
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"It has been recently identified that by acting directly on Rheb, which is the direct downstream target of TSC2 and upstream mTOR activator, the hypoxia-inducible Bnip3, a Bcl-2 homology 3 domain-conta[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18953439
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"Experimental data linking mutations to critical residues in the proteins suggests that Rheb is only able to activate mTOR when in its GTP bound state."
26319900
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"The Rheb activates mTOR by antagonizing its endogenous inhibitor FKBP38 XREF_BIBR."
22457718
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"At the lysosome surface, the small GTPase Rheb activates mTOR, and active mTORC1 promotes anabolic processes and inhibits autophagy [XREF_BIBR]."
28656016
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"Rheb is a small GTP binding protein that activates mTOR in its GTP bound form, whereas Rheb and PI3K converge to activate mTOR to stimulate cell growth and inhibit autophagy XREF_BIBR."
21959043
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"Rheb activation of mTOR and S6K1 signaling."
16757352
sparser
"Amino acids promote the recruitment of mTOR to the lysosomal surface, where mTOR is activated by RHEB."
| PMC
sparser
"Activated Rheb binds and activates the mTOR kinase to constitutively drive the TOR pathway [ xref , xref ]."
27034171
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"Emerging quick and effective antidepressants are now available based on RHEB mediated mTOR pathway which is showing an effect on treatment-resistant subjects [40, 41]."
32680568
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"The TSC is a GTPase activating factor that antagonizes the function of the small GTPase rheB, which is required to activate mTOR in response to nutrients."
22319467
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"Thus, Rheb appears to activate mTOR signaling within the time frame of its association with the ER and Golgi.Both Raptor and mTOR have previously been reported to be situated on the endomembrane [23]."
16631613
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"The functions of Akt in the regulation of autophagy have not been fully clarified, and Akt is known to phosphorylate and inhibit TSC1/2, thus leading to stabilization of Rheb GTPase, which in turn activates mTOR, resulting in the inhibition of autophagy [2, 78]."
29872222
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"The positive and negative control of TORC1 activity is exerted through the TSC1 : TSC2 complex, whose TSC2 subunit serves as a GAP for the small GTPase Rheb, which activates mTOR."
18692468
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"Thus, when insulin and IGFs are present, TSC is inactive, and Rheb retains GTP and activates mTOR."
19796712
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"Rheb mediates the activation of mTOR 20, and mTOR is activated in Notch dependent malignancies 65, and therefore this study suggests a potential role for the Rheb-Notch-Rheb loop in mTOR activation in non TSC malignancies without identified TSC1/2 mutations."
29184052
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"However, it should be noted that our findings do not rule out that other pathways or cell types exist where a PAM mediated ubiquitination of TSC2 causes mTOR activation.According to previous reports s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19000755
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"Rheb CA expression increases mTOR activity in newborn neurons in vivo."
23392671
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"Our proteomic data also suggests that the mTORC1 pathway is activated, as shown by the increased expression of several proteins in the mTOR pathway at 12 hpi, including the mTOR activator Rheb (XREF_SUPPLEMENTARY)."
24945378
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"Moreover, RHEB p.Y35L-expressing, GFP-positive neurons featured enhanced phosphorylated S6 staining (Fig. 3c, e) and an increased soma size (Fig. 3c, d, f, g), indicating that the RHEB p.Y35L mutation induces aberrant mTOR activation and cytomegalic neurons in vivo.Importantly, 1-month-old mice subjected to embryonic expression of RHEB p.Y35L exhibited spontaneous tonic-clonic seizures (Supplementary Video 1), whereas mice with embryonic expression of the control vehicle vector or wild-type RHEB demonstrated no such phenomena."
31337748
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"In addition, the combination of Rheb overexpression and artificial mTORC1 targeting to LEs by means of a modified component of mTORC1 fused with a LE-targeting motif strongly activated mTOR."
34247625
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"During amino acid deprivation, even potent upstream activators of Rheb fail to activate mTOR."
20870173
eidos
"Activation of TSC1 / TSC2 complex decreases MTOR activity by inhibiting RHEB , a positive MTOR regulator ."
36239373
sparser
"GTP-bound Rheb activates mammalian target of rapamycin complex 1 (mTORC1), which plays a conserved role in the regulation of cell growth, proliferation, survival and autophagy activation ( xref )."
34950657
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"Rheb, in its GTP bound form, is an activator of mTOR."
| PMC
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"In conclusion, dissociation of PRAS40 from mTORC1 and enhanced mTORC1 substrate binding results from Akt and mTORC1 activation and makes little or no contribution to mTORC1 signaling, which rather is determined by Rheb activation of mTOR catalytic activity, through mechanisms that remain to be fully elucidated."
21914810
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"Mechanistically, the TSC2 subunit serves as a GTPase activating protein (GAP) for the small GTPase protein Rheb, which activates the mTOR when it is GTP bound [XREF_BIBR, XREF_BIBR]."
19101635
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"The effect of Akt on mTOR is indirect : Akt inhibits the tuberous sclerosis complex (TSC) proteins 1 and 2, which act as a GTPase activating protein (GAP) to inhibit the small G protein Ras homolog enriched in brain (Rheb) which activates mTOR signaling."
21798082
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"Rheb in its GTP form activates the kinase mTor, which in turn stimulates protein synthesis by several mechanisms.Thus, AS250 and tuberin resemble each other in that both are substrates for Akt and con[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16490346
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"Rheb may activate mTOR kinase activity via direct binding [XREF_BIBR] and this effect has been mimicked in in vitro mTORC1 kinase assays [XREF_BIBR, XREF_BIBR]."
24303063
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"In summary, we have found that inhibition of Rce1- and Icmt catalyzed modifications does not prevent Rheb activation of mTOR, and that FTS inhibits mTOR through a mechanism that does not involve Rheb inhibition."
19838215
sparser
"Under nutrient-rich conditions, mTOR is mainly activated through a signaling cascade involving activation of class I PI3K/Akt, phosphorylation of tuberous sclerosis complex 2 (TSC2), and activation of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24559917
sparser
"For example, the TSC1/TSC2 complex inhibits mTOR functions by inactivating Rheb; Rheb binds and activates mTOR only when the former is in its GTP-bound form. xref The phosphoinositide-3-kinase (PI3K)-Akt pathway activates mTOR by Akt-mediated phosphorylation of TSC2, followed by disassembly and inhibition of the TSC1/TSC2 complex. xref , xref The extracellular signal-related kinase (ERK) stimulates mTOR activation by either directly phosphorylating TSC2 or by inducing TSC2 phosphorylation via its two downstream effectors, ribosomal S6 kinase (RSK) and DAPK. xref – xref Finally, AMP-activated protein kinase (AMPK) phosphorylates TSC2 and stabilizes the TSC1/TSC2 complex, thereby inhibiting Rheb-mediated activation of mTOR. xref AMPK can also regulate mTOR function in a TSC-independent manner by directly phosphorylating Raptor, an essential component of mTORC1, to inhibit mTOR activity. xref Notably, TSC1 and 2, PI3K, and Akt are all subject to mutation in human tumors."
21967333
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"Akt activation leads to phosphorylation and inhibition of tuberous sclerosis protein complex, which in turn results in subsequent engagement of Ras homolog enriched in brain to activate mTOR."
23028614
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"RHEB promotes allosteric activation of mTOR whereas PRAS40 blocks substrate recruitment sites."
29305496
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"This dissociation reduces the inhibitory function of the TSC1 and TSC2 complex on GTPase Rheb thus enabling the activation of the mTOR complex 1."
20616901
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"XREF_BIBR, XREF_BIBR Growth factors, such as insulin, activate mTORC1 through a well established signaling pathway involving the class 1A PI-3 Kinase, Akt, the TSC1/2 complex, and the GTPase Rheb, which binds to and directly activates mTOR."
20436274
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"Despite progress in the understanding of mTor signaling, there are no in vivo studies that indicate whether Rheb1 or Rheb2 is necessary to activate mTor signaling."
21238928
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"Normally, NMDAR activation leads to the degradation of the small GTPase Rheb, which prevents mTOR activation."
34566558
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"Our Rheb overexpression data are consistent with this hypothesis, because mTOR signaling in Rab5CA expressing cells is not rescued by constitutive hyperactivation of endogenous Rheb in TSC2-/- MEFs, but is rescued by overexpression of Rheb."
20053679
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"MTOR activation by constitutively active Rheb alters circadian rhythms in hepatocytes."
29750810
sparser
"We mapped the mutations onto the crystal structures of both the apo and RHEB-activated mTOR proteins ( xref )."
34538873
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"A recent study examining both signaling pathways found that ketamine increased BDNF by generating nitric oxide, leading to the stabilization of Nitrergic Rheb, a small G protein that enhances mTOR signaling."
27449797
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"Akt, Tuberin and Rheb activate mTOR when it is part of a protein complex called mTORC1 (mTOR complex 1), which is exquisitely sensitive to the drug rapamycin."
19176818
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"Additionally, PLD1, but not PLD2, was shown to be required for the activation of mTOR by Rheb [XREF_BIBR]."
20399893
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"Then the activated Rheb promotes mTOR complex 1 (mTORC1) to phosphorylate p70S6 and 4E binding protein1 (4EBP1), resulting in dysregulation of protein synthesis and cell survival [XREF_BIBR]."
24252186
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"Therefore, we dissected that circMYLK mediated tumor facilitating effect in CC depended on RHEB induced mTOR signaling activation through sponging miR-1301-3p."
32547198
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"On the other hand, activation of mTOR by isometric contraction or through overexpression of Rheb enhanced mTOR signaling and rescued the immobilization-induced drop in protein synthesis and muscle atrophy [23]."
32635462
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"The Rheb activates mTOR by antagonizing its endogenous inhibitor FKBP38."
19336571
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"Thus, rescue of HD phenotypes through Rheb mediated activation of mTOR in HD striatum appears somewhat contradictory in the face of previously published data."
25771431
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"Overexpression of Rheb, which activates mTOR independently of mTOR localization, rescued mTORC1 signaling in cells expressing Rab5CA, whereas hyperactivation of endogenous Rheb in TSC2-/- MEFs did not."
20053679
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"A number of studies establish that one of the functions of Rheb is to activate mTOR leading to growth."
25429186
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"Rheb leads to activation of mTOR through an unknown mechanism."
22724089
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"Rheb has been shown to bind directly to the kinase domain of mTOR and activate mTOR kinase activity in a GTP dependent manner [XREF_BIBR]."
21894244
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"Tuberous sclerosis complexes 1 and 2 (TSC1 and TSC2; also known as Hamartin and Tuberin) form a heterodimeric protein complex to control mTOR signalling by integrating different signalling pathways : TSC1 and TSC2 complex functions as a GTPase activating protein to inhibit the activity of Rheb, a small GTPase protein that activates mTOR activation XREF_BIBR XREF_BIBR."
27416896
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"The function of Rheb is to bind to and activate mTOR [4] and thus, it is essential for coupling all upstream signals to this pathway [5,6]."
26319900
reach
"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."
17018601
sparser
"The positive and negative control of TORC1 activity is exerted through the TSC1:TSC2 complex, whose TSC2 subunit serves as a GAP for the small GTPase Rheb, which activates mTOR ( xref ; xref ; xref )."
18692468
signor
"Rheb stimulates the phosphorylation of mtor and plays an essential role in regulation of s6k and 4ebp1 in response to nutrients and cellular energy status."
20006481
sparser
"The TSC complex naturally inhibits a protein termed Rheb (Ras homolog enriched in brain) that activates mTOR [ xref ]."
27525138
sparser
"Akt1, in turn, activates mTORC1 by inhibiting the GAP TSC1/2 complex, thus activating the GTPase Rheb, which activates mTOR."
20495773
sparser
"The role of PLD in mTOR signaling was further clarified when it was shown that PLD1, but not PLD2, was a downstream effector of Rheb (Ras homolog enriched in brain) activation of mTOR by physically interacting with Rheb in a GTP-dependent manner ( xref )."
20154608
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"Taken together, these data suggest that Rheb activation of mTOR is more dependent on farnesylation than on Rce1- and Icmt catalyzed modifications."
19838215
reach
"Rheb activates mTOR pathway."
20932898
sparser
"The positive and negative control of mTORC1 activity is exerted through the TSC1:TSC2 complex, whose TSC2 subunit serves as a GAP for the small GTPase Rheb, which activates mTOR ( Corradetti and Guan,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18692468
sparser
"MTORC1 activation requires dual inputs, one from the extracellular environment, typically mediated by growth factor-PI3K-Akt-TSC1/2-Rheb signaling, and a second from intracellular nutrient availability, typically conveyed by amino acid-mediated activation of the Ragulator-Rag complex that recruits mTORC1 to lysosomal membranes, where mTOR is activated by GTP-binding protein Rheb ( xref )."
26147685
reach
"The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is activated by the small G-protein, Ras homolog enriched in brain (RHEB-GTPase)."
| PMC
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"Therefore, these findings are important and confirm that Rheb overexpression specifically promotes mTOR rather than PI3K signaling."
12906785
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"Importantly, PLD mediates activation of mTOR by Rheb because knockdown of PLD1 by shRNA significantly inhibited phosphorylation of the mTOR substrate S6K in response to overexpression of Rheb in cells."
19166931
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"Therefore, it is likely that Rheb enhances nutrient mediated signaling through mTOR.To decisively determine whether Rheb positively activates mTOR signaling, we made use of a rapamycin resistant mutan[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12906785
reach
"The positive and negative control of mTORC1 activity is exerted through the TSC1 : TSC2 complex, whose TSC2 subunit serves as a GAP for the small GTPase Rheb, which activates mTOR (Corradetti and Guan[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18692468
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"More recently, Rheb was shown to activate mTOR in vitro, thus providing conclusive evidence that Rheb is an activator of mTOR [XREF_BIBR, XREF_BIBR]."
25429186
sparser
"Renal mTOR activation in poorly controlled diabetes may result from a combination of AKT inhibition of tuberous sclerosis complex 2, hyperglycemia-induced AMPK inhibition, and increased glucose uptake through glucose transporter 1, in which the resulting increased glycolysis and activation of GAPDH can lead directly to Rheb activation of mTOR by reducing Rheb binding to GAPDH ( xref , xref )."
24705402
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"As shown in XREF_FIG A, we confirmed that the overexpression of Rheb in immobilized muscles was sufficient to induce the activation of mTOR signaling, as revealed by an increase in the T389 phosphorylation of co-transfected GST-p70."
26092121
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"XREF_BIBR, XREF_BIBR The gene products of TSC1 (hamartin) and TSC2 (tuberin) form a single signaling complex that functions to negatively regulate the small RAS like protein, Ras homolog enriched in brain (Rheb), which in turn binds to and activates mTOR."
18952585
reach
"The pathway from PI-3 kinase to TOR is well described, proceeding through Akt inhibition of the Tuberous Sclerosis complex, a GTPase activating protein for the ras like GTPase Rheb, and Rheb activation of mTOR complex 1."
22125066
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"MTOR is directly activated by the small guanosine triphosphatase Ras homolog enriched in brain (Rheb), in a farnesylation dependent manner."
17914450
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"MTORC1 translocates to the lysosome membrane in response to a stimulus, where the binding of Rheb activates mTOR."
33828530
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"First, we wanted to confirm in our assays that Rheb activation of mTOR is dependent on farnesylation."
19838215
sparser
"Rheb-GTP activates mammalian target of rapamycin (mTOR), but the hamartin-tuberin complex suppresses mTOR activity by converting Rheb-GTP to Rheb-GDP xref ."
30425292
sparser
"Tuberin contains a GTPase activating protein (GAP) domain that has been shown to stimulate the Ras homolog enriched in brain (RHEB) GTP-binding protein [ xref ], which in turn activates mTOR complex 1."
21806479
sparser
"Mechanistically, the TSC2 subunit serves as a GTPase activating protein (GAP) for the small GTPase protein Rheb, which activates the mTOR when it is GTP-bound [ xref , xref ]."
19101635
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"Tsc2 accelerates the inactivation of Rheb, and Rheb activates mTOR, a kinase with important regulatory functions in translation, transcription, autophagy and other cellular processes."
24662006
reach
"Together these proteins form a heterodimer that inhibits Rheb (Ras homolog expressed in brain), the GTPase that activates the mTOR pathway [XREF_BIBR]."
26579319
sparser
"The mechanisms that activate mTOR in the absence of Rag-Ragulator activity remain to be elucidated, but there is evidence that Rheb can localize and activate mTOR at the lysosome in conditions when the Rag proteins are inactive ( xref )."
26774477
reach
"The results indicated that overexpression of Rheb induces a significant increase in mTOR signaling in skeletal muscle myoblasts (XREF_FIG)."
20668162
sparser
"Activated mTOR further phosphorylates ribosomal p70 S6 kinase (S6K1), eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), and Akt, controlling cell proliferation, growth, and survival. xref , xref Activated PDK1 also positively regulates S6K1. xref Studies have placed tuberous sclerosis complex (TSC) 1/2 as a modulator between PI3K/Akt and mTOR. xref - xref The TSC1/2 complex acts as a repressor of mTOR function. xref - xref TSC2 has GTPase-activating protein (GAP) activity towards the Ras family small GTPase Rheb (Ras homolog enriched in brain), and TSC1/2 antagonizes the mTOR signaling pathway via stimulation of GTP hydrolysis of Rheb. xref - xref Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38, xref though this remains controversial. xref The TSC can also be activated by energy depletion through the activation of AMP-activated kinase (AMPK). xref AMPK responds both to changes in AMP concentration and to changes in the ratio of AMP to ATP. xref An increased AMP to ATP ratio allows AMPK phosphorylation and activation. xref This, in turn, activates the TSC, which catalyzes the conversion of Rheb-GTP to Rheb-GDP and thus inhibits mTOR. xref AMPK can also be phosphorylated and activated by the calcium- and calmodulin-dependent protein kinase kinase-β (CaMKK-β) in response to alterations in intracellular calcium homeostasis. xref In addition, AMPK may be activated by oxidative stress. xref "
20142804
trips
"It has recently been shown that Rheb activates mTOR by binding to its endogenous inhibitor FKBP38 and preventing it from association with mTOR."
18658153
reach
"Since RHEB is the canonical activator of mTOR, this finding is consistent with other reports that have highlighted mTOR as a main regulator of cell size XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
29051493
reach
"AKT is responsible for the inhibition of negative regulators of mTOR, such as tuberous sclerosis complex (TSC1/2), whilst pyruvate dehydrogenase kinase 1(PDK1) induces the mTOR activator Rheb (Ras homolog enriched in brain), thereby releasing the mTOR complex to phosphorylate its targets (Perluigi et al., 2015)."
31231176
reach
"Active Rheb directly activates the mTOR kinase by altering substrate affinities."
23485365
sparser
"Rheb-GTP normally activates the rapamycin-sensitive mTOR complex, called mTORC1, in which the mTOR kinase is associated with the proteins raptor and GβL ( xref , xref )."
19150975
eidos
"Specifically , key metabolites lead to the activation of the Rag proteins , which recruit mTORC1 to the lysosome so that Rheb can activate mTOR ( Sancak et al ., 2008 ) ."
30661928
reach
"MTOR signaling, including Ras homolog enriched in brain (Rheb), rapamycin insensitive companion of mTOR (Rictor) and ribosomal protein S6 kinase B2 (S6K2), was investigated by western blotting and qPCR, and insulin responsiveness was evaluated by glucose uptake and phosphorylation of insulin receptor substrate-1 (p-IRS1)."
33159675
reach
"Combined, these results indicate that 1) Rheb induces hypertrophy through a rapamycin sensitive mechanism, 2) mTOR is the rapamycin sensitive element in skeletal muscle that confers Rheb induced hypertrophy, and 3) mTOR kinase activity is necessary for the Rheb induced hypertrophic response."
20668162
reach
"Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38 [XREF_BIBR], though this remains controversial [XREF_BIBR]."
21195169
sparser
"Furthermore, studies in nonskeletal muscle cells have shown that Rheb activates mTOR through a PI3K/PKB-independent mechanism ( xref ; xref )."
20668162
sparser
"Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38 [ xref ], though this remains controversial [ xref ]."
20491627
eidos
"Rheb , in its GTP-bound form , is an activator of mTOR ."
| PMC
reach
"To determine whether Rheb activates mTOR- or PI3K mediated signaling, we coexpressed Rheb with hemagglutinin (HA)-tagged 4E-BP1 in the presence of either rapamycin or wortmannin to inhibit mTOR or PI3[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12906785
reach
"Instead, we found that FTS blocked Rheb activation of mTOR, but this effect was independent of inhibition of Rheb or of any other prenylated protein."
19838215
reach
"Looking to the future, there is still a need to elucidate how mTOR conformational changes that are induced by Rheb are either maintained or terminated and how such steps contribute to the regulation of mTORC1 signaling."
32518628
reach
"Indeed, mTOR can be activated by RHEB either on the surface of the peroxisome [198]–in response to reactive oxygen species (ROS)–or on the surface of the lysosome [89]–in response to amino acids."
33933601
sparser
"MTOR is activated by the GTPase Rheb which in turn is controlled by the TSC1/TSC2 complex."
20616901
reach
"One of the major effects of the activation of mTOR by Rheb is to suppress autophagy [XREF_BIBR]."
27034171
sparser
"Rheb activates mTOR by antagonizing its endogenous inhibitor, FK506 binding protein 38 (FKBP38) [ xref ], though this remains controversial [ xref ]."
23272914
sparser
"Rheb, in its GTP-bound state, can activate mTOR."
32093152
reach
"XREF_BIBR, XREF_BIBR The inactivation of TSC1/2 relieves inhibition on the RAS family GTP binding protein RHEB, which subsequently activates mTOR by antagonizing the endogenous mTOR inhibitor FKBP38."
19610618
reach
"Thus, while these CAAX modifications are necessary for proper subcellular localization, Rheb activation of mTOR is not impaired in the absence of Rce1 or Icmt function."
19838215
reach
"To test whether over-expression of Rheb could upregulate mTOR activity in vitro, we constructed a Myc tagged wild-type (wtRheb) and a HA tagged, constitutively active mutant Rheb (caRheb)."
27264357
reach
"In summary, overexpression of Rheb activates mTOR signaling via a PI3K and PKB independent mechanism and is sufficient to induce skeletal muscle hypertrophy."
20668162
sparser
"The above results suggested that Rce1- and Icmt-catalyzed modifications are required for Rheb localization, but not for Rheb activation of mTOR."
19838215
reach
"Membrane dependent modulation of the mTOR activator Rheb : NMR observations of a GTPase tethered to a lipid-bilayer nanodisc."
23409921
reach
"Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38 [XREF_BIBR], though this remains controversial [XREF_BIBR]."
20491627
bel
"Meanwhile, raptor interacts with active Rag GTPase heterodimers in which GTP-bound RagA or RagB (very similar to RagA) associates with GDP-bound RagC or RagD (similar to RagC), and raptor targets mTOR to lysosome surface where mTOR could be activated by its activator Rheb on the lysosomes."
26702100
sparser
"While constitutively active AKT is as capable as PTEN −/− xref , xref , recent data demonstrate that direct activation of mTOR by constitutively active Rheb or downstream modulation of the mTORC1 effectors E4BP or S6K1 fail to fully mimic the regenerative effect xref , xref , xref , xref ."
31453382
reach
"Siah1 degrades Rheb leading to reduced mTOR signaling, while ketamine, conversely, stabilizes Rheb which enhances mTOR signaling."
26782056
reach
"When in its GTP bound state, Rheb has been reported to directly activate mTOR signaling."
27909410
reach
"The small GTPase Ras homolog enriched in the brain (Rheb) can activate mammalian target of rapamycin (mTOR) and regulate the growth and cell cycle progression."
32920594
sparser
"In its GTP-bound state Rheb activates the rapamycin-sensitive mTOR complex (mTORC1), a step which is inhibited by FTIs ( xref )."
29760048
eidos
"Conclusion It was unveiled that circMYLK sponged miR-1301-3p to promote RHEB expression , which resulted in mTOR signaling activation and CC cell malignant growth ."
32547198
reach
"Another study suggested that Rheb activates the mTOR complex by antagonizing its inhibitor FK506 binding protein 38 (FKBP 38)."
21035549
reach
"In the absence of polycystin-1, disinhibition of Rheb results in activation of mTOR and increased cell growth."
19430332
reach
"In many metazoan organisms, growth factor availability is also integrated into the activation of mTORC1 via regulation of the nucleotide binding state of Ras homolog enriched in brain (Rheb), a small GTPase that binds to and allosterically activates the mTOR kinase when it is part of mTORC1 XREF_BIBR, XREF_BIBR."
32518628
reach
"The above results suggested that Rce1- and Icmt catalyzed modifications are required for Rheb localization, but not for Rheb activation of mTOR."
19838215
reach
"Rheb activates mTOR signaling, but the activities of TSC1 and TSC2 complexes decrease in mTOR activation."
26484025
reach
"Ras homolog enriched in the brain (RHEB), which activates mTOR complex 1, inhibits the transportation of protein aggregates to aggresomes by dissociation of the dynein and aggregate complex [XREF_BIBR]."
33670947
reach
"To determine whether the direct activation of mTOR by Rheb also enhances axonal growth capacity in vitro, we cultured DRG neurons from adult rats and measured axonal outgrowth 3 days following Rheb or GFP lentiviral transduction (XREF_FIG)."
27264357
reach
"Rheb mediated activation of mTOR causes phosphorylation, and thus activation of, S6 ribosomal protein."
27458339
sparser
"Although Rheb2 can activate mTor when over expressed in vitro ( xref ), Rheb2 is not required for organismal viability, and is not essential for mTORC1 or mTORC2 signaling, or myelination ( xref ) in brain."
21238928
reach
"While in conditions of rich growth factors and nutrients, FKBP_C domain may interact with Rheb (Ras homolog enriched in brain)-GTP to activate the mTOR downstream signaling pathway by releasing mTOR from FKBP38."
25049623
sparser
"Akt, Tuberin and Rheb activate mTOR when it is part of a protein complex called mTORC1 (mTOR complex 1), which is exquisitely sensitive to the drug rapamycin ( xref ; xref ; xref )."
19176818
sparser
"Reconstituted mTOR activation by constitutive Rheb proved cytoprotective [ xref ]."
34215308
reach
"XREF_BIBR Exogenous expression of Rheb enhanced phosphorylation of mTOR effectors S6K and 4E-BP1 in a rapamycin dependent manner, while co-expression of Rheb with TSC2 : TSC1attentuates Rheb mediated mTOR activation."
20146692
reach
"Activated Akt inhibits TSC (tuberous sclerosis complex) 1/2, thereby relieving its inhibition of Rheb (Ras homologue enriched in brain), allowing Rheb activation of mTOR."
23421405
sparser
"Importantly, the impact of Rheb on B-Raf/C-Raf heterodimerization and kinase activity are rapamycin-insensitive, indicating that they are independent of Rheb activation of the mammalian target of rapamycin-Raptor complex."
16803888
reach
"Both mTOR complexes are stimulated by Ras homolog enriched in brain (RHEB) which is downstream from insulin, growth factor and nutrient signaling pathways."
28768896
reach
"XREF_BIBR Given that Rheb is able to bind the kinase domain of other phosphatidylinositol-3 kinase like kinase (PIKK) family members such as ataxia telangiecstasia mutated (ATM) and ataxia telangiecstasia and Rad3 related (ATR), XREF_BIBR structural studies examining the physical interaction between Rheb and mTOR could provide helpful insight into how Rheb activates mTOR."
29296509
sparser
"Active Rheb directly activates the mTOR kinase by altering substrate affinities ( xref )."
23485365
sparser
"Rheb activates mammalian target of rapamycin complex 1 (mTORC1), which causes an increase in protein translation by phosphorylating its two best characterized targets S6K (p70S6 kinase) and 4EBP (eIF-4E-binding protein)."
23497627
reach
"The mechanisms by which mTORC1 is activated by amino acids are less clear but a number of studies have shown that the binding of Raptor to the Rag GTPases, a family of four related small GTPases XREF_BIBR, is necessary for mTOR to localize onto the lysosome where mTOR is activated by its upstream activator Rheb XREF_BIBR, XREF_BIBR,."
24740400
reach
"Rheb, in its GTP-bound state, can activate mTOR."
32093152
sparser
"In these conditions, MTOR is activated by RHEB (Ras homolog enriched in brain; in its GTP-bound form) and phosphorylates ULK1 at the inhibitory Ser757 site."
25759175
reach
"Expression of a constitutively active Rheb enhanced mTOR activity and increased the fiber size in VCP-IBM mouse skeletal muscle."
23250913
reach
"A recent study has shown that mTOR is required to interact with late endosomes that are enriched in TMEM127 proteins, as binding to the mTOR activators Rheb and PA is necessary for its activation."
28187001
reach
"Moreover, genes that negatively regulate the mammalian target of rapamycin (mTOR), the main regulator of autophagy, such as AMPK, LKB1, PTEN and TSC1/2 induce autophagy while, conversely, oncogenes that promote mTOR signaling, such as class I PI3K, AKT, Ras and RHEB inhibit autophagy [XREF_BIBR, XREF_BIBR]."
29783720
reach
"In contrast, Cul4-DDB1-Fbw5 E3 ligase regulates TSC1 and TSC2 complex turnover increasing in the constitutive activation of the downstream mTOR activator RHEB."
28923280
reach
"These results suggested Rheb activated mTOR signaling."
25799586
reach
"We reveal that Rheb specifically activates mTOR mediated signaling rather than cell signaling through MEK and ERK and PI3K, as shown by Rheb mediated activation of S6K1 but not Akt or RSK1."
12906785
sparser
"In particular, the activation of mTOR by Rheb is not well known but future studies may shed light on this situation ()."
26341051
reach
"The tuberous sclerosis complex (TSC) includes TSC2, a GAP inactivating the GTPase Rheb (Inoki et al., 2003; Tee et al., 2003), which in turn activates mTOR (Long et al., 2005; Sancak et al., 2007)."
29625033
reach
"However, Rheb mediated activation of mTOR did not impart a meaningful protection against BITC induced cleavage of LC3 (XREF_FIG), LC3 puncta (XREF_FIG) or cell growth inhibition (XREF_FIG)."
22457718
reach
"Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory axons after spinal cord injury by activating downstream effectors of mTOR."
37282486
reach
"MTOR activity is upregulated by Rheb (Ras homology enriched in brain), a Ras GTPase superfamily member that acts to promote cell growth."
29551131
sparser
"The tuberous sclerosis complex (TSC) includes TSC2, a GAP inactivating the GTPase Rheb (), which in turn activates mTOR ()."
29625033
sparser
"Activated Akt inhibits TSC (tuberous sclerosis complex) 1/2, thereby relieving its inhibition of Rheb (Ras homologue enriched in brain), allowing Rheb activation of mTOR ( xref ; for review, see Avruch et al., xref )."
23421405
reach
"115 Moreover, RHEB mediation of mTOR activity is necessary for OPC differentiation into myelinating OLs."
28934193
reach
"MTORC1 activity is negatively regulated by the TSC1/2 complex, which inhibits Ras homologue enriched in brain (Rheb), a small guanosine triphosphatase (GTPase) that activates mTOR, via its GTPase activating protein (GAP) activity."
24474199
sparser
"Rheb-GDP is the inactive form whereas Rheb-GTP directly activates mTOR."
24400038
reach
"In the endomembrane, Rheb, which is a Ras related GTP protein, activates mTOR, although the detailed mechanism of its action remains unclear."
23197407
reach
"RHEB stimulates the protein kinase mTOR, which results in activating phosphorylation of the mTOR substrates S6 kinase (S6K) and eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) XREF_BIBR, XREF_BIBR, which is consistent with RHEB being essential for cell growth and cell cycle progression in D. melanogaster 116."
22020205
reach
"Furthermore, we found that the Icmt inhibitor cysmethynil did not block Rheb activation of mTOR (data not shown)."
19838215
reach
"The GTP bound active form of Rheb strongly stimulates mTOR and its downstream targets, such as the ribosomal S6 kinase 1 (S6K1) and the eukaryotic initiation factor 4E binding protein (4EBP-1) [XREF_BIBR - XREF_BIBR]."
20412061
reach
"Thus, when combined, these data indicate that overexpression of Rheb induces mTOR signaling through a PI3K and PKB independent mechanism in adult skeletal muscle in vivo and that the effects of Rheb on mTOR seem to be specific to the mTORC1 complex."
20668162
reach
"Activated Rheb stimulates mTOR complex 1 (mTORC1) that finally leads to an enhancement of general translation with an increase in protein synthesis and cell growth."
22065949
sparser
"TSC1/2 negatively regulates Rheb, which directly activates mTOR."
23392671
sparser
"When the TSC complex is inhibited by AKT, RHEB activates mTOR [ xref ]."
27860216
sparser
"Furthermore, we found that the Icmt inhibitor cysmethynil did not block Rheb activation of mTOR (data not shown)."
19838215
sparser
"Therefore, we dissected that circMYLK mediated tumor-facilitating effect in CC depended on RHEB-induced mTOR signaling activation through sponging miR-1301-3p."
32547198
sparser
"The small G-protein Rheb activates the mechanistic target of rapamycin complex 1 (mTORC1) in response to growth factor signals."
29416044
reach
"The activation of Rheb allows mTor to be activated through association with raptor and other TORC1 complex members, stimulating TOR dependent mRNA translation through p70S6Kinase, and cap dependent translation thorough inhibition of the eiF4e repressor, 4E-BP."
20176047
sparser
"MTOR is activated by the small guanosine triphosphatase Ras homolog enriched in brain (Rheb) ( Castro et al. , 2003 ; Garami et al. , 2003 ; Inoki et al. , 2003 ; Saucedo et al. , 2003 ; Stock[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17914450
reach
"Experimental data linking mutations to critical residues in the proteins suggest that Rheb is only able to activate mTOR when in its GTP bound state [10]."
26319900
reach
"Since Ras homolog enriched in brain (Rheb) plays critical roles in the activation of mTOR, we determined whether Rheb mediates high glucose activated mTOR signaling by gene silencing of Rheb."
25016145
sparser
"Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38 [ xref ], though this remains controversial [ xref ]."
21195169
reach
"Rheb is the upstream activator of mTOR."
29750810
sparser
"MTOR activation by constitutively active Rheb alters circadian rhythms in hepatocytes."
29750810
reach
"Upregulation of the GTPase RHEB induces mTOR activation that protects DTCs from apoptosis [XREF_BIBR]."
32260071
reach
"The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is activated by the small G-protein, Ras homolog enriched in brain (RHEB-GTPase)."
34445471
reach
"Overexpression of Rheb activates mTOR signaling via a PI3K and PKB independent mechanism and is sufficient to induce skeletal muscle hypertrophy."
20668162
sparser
"This process requires PI3-K/Akt-dependent activation of the small G protein Rheb, which activates mTOR and its downstream effector kinase S6K (the p70 S6 kinase) that serine-phosphorylate IRS-1, there[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18498745
sparser
"Furthermore, Tsc2 deficiency and hyperactive Rheb constitutively activated mTOR and inhibited ephrin-induced growth cone collapse."
20062052
reach
"Overexpression of Rheb due to a TSC1 or TSC2 mutation leads to increased mTOR activation and excessive cell growth and proliferation."
28367137
sparser
"The pathway from PI-3 kinase to TOR is well described, proceeding through Akt inhibition of the Tuberous Sclerosis complex, a GTPase activating protein for the ras-like GTPase Rheb, and Rheb activation of mTOR complex 1 ( xref )."
22125066
reach
"Rheb stimulated the activation of mTOR with an essential role in the regulation of S6K and 4EBP1 [XREF_BIBR]."
26275051
reach
"The GTP bound form of Rheb lies immediately upstream of mTORC1 to stimulate mTOR kinase activity; however, just upstream to Rheb is the tumor suppressor complex tuberous sclerosis 1/2 (TSC1/2) that negatively regulates mTORC1 by converting Rheb to the inactive GDP bound form."
24329799
reach
"To accomplish the goal of this study, overexpression of Rheb was used as a means to induce a PI3K and PKB independent activation of mTOR signaling."
20668162
reach
"In this study, we determined that, in skeletal muscle, overexpression of Rheb stimulates a PI3K and PKB independent activation of mTOR signaling, and this is sufficient for the induction of a rapamycin sensitive hypertrophic response."
20668162
sparser
"Specifically, key metabolites lead to the activation of the Rag proteins, which recruit mTORC1 to the lysosome so that Rheb can activate mTOR ( xref )."
30661928
sparser
"To determine whether the direct activation of mTOR by Rheb also enhances axonal growth capacity in vitro , we cultured DRG neurons from adult rats and measured axonal outgrowth 3 days following Rheb or GFP lentiviral transduction ( xref )."
27264357
reach
"The regulation of mTORC1 is dependent on tuberous sclerosis complex 1 and 2 (TSC1 and TSC2), of which TSC2 acts as a GTPase activating protein for the small GTPase Rheb, which negatively controls Rheb and activates mTOR [XREF_BIBR, XREF_BIBR]."
33530433
reach
"The increased expression of Rheb then activated mTOR pathway."
26213322
sparser
"The mTORC1-Rag interaction is thought to bring mTOR into proximity of the Rheb GTPase that activates mTOR in response to growth factor and energy-dependent signals ( xref )."
29626653
reach
"While forced expression of Rheb activates mTOR and S6K that in turn serine phosphorylate IRS-1, elevated levels of Fbw8 promote the assembly of the CUL7 E3 ligase that mediates the ubiquitination of I[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18498745
reach
"XREF_BIBR - XREF_BIBR Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38, XREF_BIBR though this remains controversial."
20142804
sparser
"Rheb is an upstream regulatory factory in mTOR signaling pathway and the Rheb-GTP can activate mTOR to advance the signals to endogenous S6K1 by phosphorylation at its residues Thr389, Thr421 and Ser 424 ( xref ; xref ; xref )."
25049623
reach
"We have studied whether Rheb is sufficient to activate mTOR signaling and promote protein synthesis and cardiac hypertrophy in adult rat ventricular cardiomyocytes (ARVC)."
18722381
sparser
"Nevertheless, the functional data showed that only the GTP-bound Rheb can activate mTOR ( xref )."
32470140
reach
"Given that the loss of Rheb in yeast mimicked nutrient starvation [23], Rheb overexpression may promote mTOR signaling through a nutrient regulated signaling pathway."
12906785
sparser
"Experimental data linking mutations to critical residues in the proteins suggest that Rheb is only able to activate mTOR when in its GTP-bound state [10] ."
26319900
reach
"S-nitrosylation of TSC2 inhibits its GAP activity by blocking the dimerization of TSC2 with its partner TSC1, thereby enhancing the GTP-dependent activity of its target Rheb to activate mTOR signaling[117]."
34789923
reach
"Furthermore, studies in nonskeletal muscle cells have shown that Rheb activates mTOR through a PI3K and PKB independent mechanism."
20668162
reach
"For instance TSC1 and TSC2 inhibits mTORC1 signaling through the inhibition of the mTOR activator Ras Homolog Enriched In Brain (Rheb); however, TSC1 and TSC2 has been demonstrated to activate mTORC2 signaling through direct contact with mTORC2 [XREF_BIBR, XREF_BIBR]."
25283550
sparser
"The small guanosine triphosphatase Rheb directly activates mTOR, and Rheb is farnesylated ( Clark et al. , 1997 ; Castro et al. , 2003 ; Li et al. , 2004 ; Basso et al. , 2005 ; Gau et al. , [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17914450
sparser
"Although it is unknown how Prom1 negatively regulates mTOR signaling in the RPE, previous studies demonstrated that inhibition of mTOR signaling increased the CD133 + subpopulations in vitro and in vivo, whereas activation of mTOR by Rheb significantly decreased CD133 expression. xref In cancer cells, a mechanistic relationship exists between CD133 and the hypoxia-inducible factor-1α, a downstream target in the mTOR signaling pathway. xref These previous observations support the presence of a molecular cross talk between Prom1 and mTOR signaling in the regulation of autophagy flux in the RPE."
28437526
reach
"Recently, Rheb was shown to interact with mTOR and raptor and activate kinase activity of mTOR [23,24]."
16837165
reach
"We propose a model whereby Rheb promotes mTOR signaling when it is in an active GTP bound form, whereas the Tuberin and Hamartin heterodimer inhibits Rheb by converting it to an inactive GDP bound sta[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12906785
reach
"We found that ATF6alpha induced Rheb, a small GTPase of the Ras family that directly activates the survival protein mTOR."
23143976
reach
"These results further confirm that the RHEB p.Y35L mutation causes FCDII by activating the mTOR pathway."
31337748
eidos
"Indeed , mTOR can be activated by RHEB either on the surface of the peroxisome [ 198 ] - in response to reactive oxygen species ( ROS ) - or on the surface of the lysosome [ 89 ] - in response to amino acids ."
33933601
reach
"Among the downstream targets of Akt is the tuberous sclerosis complex 2 (TSC2), which is—together with TSC1—located on the lysosomal membrane, from which it subsequently dissociates to act as a GAP for the Ras-related small GTPase, Rheb, which in turn activates mammalian target of rapamycin complex 1 (mTORC1)."
34249909
sparser
"Indeed, mTOR can be activated by RHEB either on the surface of the peroxisome [ xref ]–in response to reactive oxygen species (ROS)–or on the surface of the lysosome [ xref ]–in response to amino acids."
33933601
sparser
"Importantly, PLD mediates activation of mTOR by Rheb because knockdown of PLD1 by shRNA significantly inhibited phosphorylation of the mTOR substrate S6K in response to overexpression of Rheb in cells."
19166931
reach
"The decreased ability of the farnesylation deficient Rheb to activate mTOR signaling suggests that farnesylation inhibitors might be effective drugs in the treatment of the TSC disease.It is likely th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12906785
reach
"Together, these results indicate that overexpression of Rheb induces mTOR signaling through a PI3K independent mechanism in C2C12 myoblasts."
20668162
reach
"Rheb is unique among members of the small GTPase family in that the regulation of its function occurs predominately through its inactivation by Rheb GAPs (e.g., TSC2) rather than its activation by Rheb guanidine exchange factors (GEFs); thus, overexpression of Rheb bypasses the requirement for PI3K activation of Akt to promote mTOR activity."
18922908
reach
"In this study, we show that Rheb like-1 protein (RhebL1) rescues mTOR signaling during nutrient withdrawal and that tuberous sclerosis complex-1 (TSC) and TSC2 impairs RhebL1 mediated signaling through mTOR."
16098514
reach
"As Rheb, in turn, activates mTOR, the TSC genes function to dampen down mTOR signaling pathway activity, and, given the role of mTOR in stimulating cell growth and proliferation, normally prevent excessive growth and proliferation."
19817806
reach
"Yang et al. [55] also showed that rapamycin enhanced the level of CD133 and stem cell associated genes in human liver tumor cell lines, whereas mTOR activation by Rheb overexpression decreases CD133."
24027431
reach
"The GTP binding protein RheB increases mTOR kinase activity XREF_BIBR, XREF_BIBR."
29628997
reach
"Overexpression of Rheb Induces mTOR Signaling through a PI3K and PKB independent Mechanism in Skeletal Muscle In Vivo."
20668162
reach
"The ability of overexpressed Rheb to rescue TOR signaling from amino-acid withdrawal may be attributable to the ability of Rheb-GTP to promote mTOR kinase activity (as shown herein) and perhaps also t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15854902
reach
"These findings suggest that the membrane localization of Rheb through farnesylation is important for Rheb to efficiently augment mTOR mediated signaling.In this study we show that Rheb functions upstr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12906785
sparser
"In addition, we found that activation of mTOR by Rheb2 or a constitutively active RagB mutant (RagB GTP ), like overexpression of p62 itself, enhances the soft agar growth of A498 cells ( xref )."
24332042
reach
"When Rheb is in its GTP bound form, it directly interacts with and activates mTORC1, but the exact mechanism by which Rheb activates mTOR is unclear."
23460185
reach
"Collectively, these in vitro studies demonstrate a link between two pathways that regulate mTOR, PLD/PA and TSC2 and Rheb, and provide further insight into a mechanism by which Rheb activates mTOR."
19166931
reach
"Furthermore, p38 has been shown to phosphorylate Raptor on the S863 residue in response to aresnite, and the activation of mTOR by Rheb overexpression is associated with an increase in S696, T706, and S863 phosphorylation [XREF_BIBR, XREF_BIBR]."
24239769
sparser
"Therefore, we investigated whether circMYLK functioned its tumor-facilitating impact in CC through a RHEB-dependent mTOR signaling activation."
32547198
reach
"The satiety hormone leptin may also be regulated by miR-155 : Adipocyte leptin expression is elevated by Rheb mediated mTOR activation XREF_BIBR."
26953132
reach
"This conclusion is reinforced by supplementary data from two studies : mice with a neo-insertion in an Mtor intron that decreases Mtor mRNA approximately 70% show a similar selective lowering of CD44 on CD4 + T cells and CD44 levels are also reduced on naive, CD62L positive T cells that are deficient for the mTOR activator Rheb or deficient for the mTOR interacting protein Rictor."
24336796
reach
"The small guanosine triphosphatase Rheb directly activates mTOR, and Rheb is farnesylated (Clark et al., 1997; Castro et al., 2003; Li et al., 2004; Basso et al., 2005; Gau et al., 2005)."
17914450
sparser
"AMPK antagonizes this Akt-induced mTOR activation by activating tumor suppressor tuberous sclerosis 2 (TSC2, tuberin), which in turn inactivates a small G-protein, Rheb, and in consequence disabled Rheb cannot activate mTOR [ xref – xref ]."
18509489
sparser
"The inactivated TSC2 fails to inactivate the RHEB-GTP (Ras homolog enriched in brain-Guanosine-5′-triphosphate) that can activate mTOR ( xref )."
22688403
reach
"Despite this, the kinase activity of mTOR has been found to be higher when it is copurified with recombinant wild-type Rheb than with inactive mutants, suggesting that the ability of Rheb to stimulate mTOR relies on its activity."
19823764
reach
"Rheb modulates mTOR complex and controls protein synthesis through the phosphorylation of 4E-BP1 and S6."
29287199
sparser
"This effect is mediated via the tuberous sclerosis complex (TSC1/TSC2), which suppresses mTOR activation by the G-protein Rheb ( xref ; xref )."
21368030
reach
"However, evidence exists that Rheb2 can also activate mTOR."
21412983
reach
"Activated Rheb activates mTOR to inhibit autophagy (see XREF_FIG) [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
33628363
reach
"Most importantly, the ability of RHEB to stimulate mTOR depends on its farnesylation XREF_BIBR, XREF_BIBR."
22020205
reach
"RHEB may activate mTOR either by directly binding to it 117 or by binding to the mTOR antagonist FKBP38 (also known as FKBP8) 118."
22020205
reach
"Although Rheb2 can activate mTor when over expressed in vitro, Rheb2 is not required for organismal viability, and is not essential for mTORC1 or mTORC2 signaling, or myelination (XREF_SUPPLEMENTARY) in brain."
21238928
reach
"In addition to these other mechanisms it has recently been reported that RHEB GTPase which stimulates mTOR activity also phosphorylates eIF2alpha attenuating protein translation [XREF_BIBR]."
27183907
reach
"As expected, 4E-BP1 was released from eIF4E upon Rheb overexpression, implying that Rheb activates cap dependent translation.The above data implies that Rheb may modulate mTOR signaling."
12906785
signor
"Rheb binds and regulates the mTOR kinase."
15854902
reach
"The association of mTOR with GTP charged Rheb increases mTOR kinase activity."
15854902
sparser
"When TSC2 is phosphorylated by MAPK1 at Ser664, TSC1/TSC2 complex is destabilized, allowing RHEB to activate MTOR."
36239373
reach
"Rheb, in its GTP bound state, can activate mTOR."
16404421
sparser
"MTOR is directly activated by the small guanosine triphosphatase Ras homolog enriched in brain (Rheb), in a farnesylation-dependent manner."
17914450
reach
"Activation of Ras and Rheb stimulated downstream mTOR and ERK pathways."
34467534
reach
"Previous work showed Rheb can signal both mTOR dependent and -independent pathways (Alves et al., 2015; Neuman and Henske, 2011; Saito et al., 2005; Tyagi et al., 2015), and we found that Rheb can sig[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27960107
reach
"Overexpression of the small G protein rheb, which greatly enhances mTOR signaling, markedly increased EGFP-HDQ74 aggregates and cell death in COS-7 cells (XREF_FIG E)."
16186256
sparser
"Rheb activates mTOR to suppress autophagy and promote transformation [ xref ]."
27034171
sparser
"Tsc2 accelerates the inactivation of Rheb, and Rheb activates mTOR, a kinase with important regulatory functions in translation, transcription, autophagy and other cellular processes."
24662006
reach
"An important regulator of RHEB activity is the TSC complex which inactivates RHEB by accelerating GTP hydrolysis, and it has been reported that the TSC2 protein cycles on and off the lysosomal surface in response to amino acid levels : when amino acids are withdrawn TSC2 translocates to the lysosomal surface where it inactivates RHEB causing the subsequent mTOR inactivation."
27725083
reach
"Rheb activates the mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cellular growth and metabolism in the Ras/PI3K/Akt/mTOR pathway."
33440168
eidos
"In its inactive form , Rheb is unable to stimulate the mammalian target of rapamycin ( mTOR ) ; hence , Tuberin indirectly prevents mTOR activity under poor growth conditions ."
30629673
reach
"There is evidence indicating that BNIP3 inhibits the mTOR pathway through RHEB (an activator of mTOR) [50], and this protein has been shown to induce cell death by autophagy which was inhibibed by 3-M[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24514040
reach
"Tuberous sclerosis complexes (TSCs) normally inhibit Rheb directed mTOR activation, and mutations in TSC proteins (TSC1-hamartin, TSC2-tuberin) constitutively activate Rheb-mTOR-pS6K and increase cell size."
27795403
reach
"Since it remained possible that FTS may disrupt Rheb interaction with mTOR, we next asked if FTS inhibits Rheb induced activation of mTOR."
19838215
reach
"These scenarios demonstrate how signals transduced through the TSC are mediated by Rheb to affect mTOR, although the precise interactions between Rheb and mTOR have not yet been entirely elucidated."
22870038
reach
"The Rheb CA -encoding vector has been used as a reliable tool to increase mTOR activity in different cell types."
23392671
sparser
"In mammalian cells, in response to AAs, the Rag GTPase complex recruits mTORC1 to lysosomes, where mTOR is activated by Rheb ( xref , xref )."
21512002
sparser
"However, evidence exists that Rheb2 can also activate mTOR (Campbell et al, xref ; Tee et al, xref ; Yuan et al, xref )."
21412983
trips
"Rheb binds directly to the amino-terminal lobe of the mTOR catalytic domain, and activates mTOR kinase in a GTP-dependent manner."
15878852
reach
"MTOR is activated by the small guanosine triphosphatase Ras homolog enriched in brain (Rheb) (Castro et al., 2003; Garami et al., 2003; Inoki et al., 2003; Saucedo et al., 2003; Stocker et al., 2003; [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17914450
reach
"Furthermore, diverse studies have demonstrated Rheb is a key activator of mTOR, which blocks autophagy at the posttranslational and transcriptional levels [XREF_BIBR]."
31998438
reach
"When compared to Rheb, the greater effect size of ca-Akt was also expected because ca-Akt has the potential to induce an increase in protein synthesis through the combined activation of mTOR signaling and the inhibition of glycogen synthase kinase-3 beta (GSK3beta), while Rheb only activates mTOR signaling."
23089927
reach
"Thus, while geranylgeranylation can not substitute for farnesylation in promoting Rheb signaling capacity, it appears to be sufficient for regulating Rheb turnover.Although the molecular mechanism of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16631613
reach
"When the hamartin and tuberin complex is not functional, elevated levels of active Rheb (Rheb-GTP) constitutively activate mTOR, ultimately resulting in abnormal protein translation."
19368729
sparser
"In this case, GTP-bound RHEB activates mTOR."
24672426
reach
"Akt phosphorylation inactivates the tuberous sclerosis complex (TSC) formed by hamartin (TSC1) and tuberin, leading to accumulation of the GTP bound form of the small G protein Rheb that activates mTOR."
17646396
reach
"First, insulin/IGF1 induces the activation of the insulin receptor substrate 1 (IRS-1)/phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) pathway, leading to GTP-loading of the mTOR activator Rheb (Hemmings and Restuccia, 2012; Hassan et al., 2013)."
34354601
reach
"ATF6 increases the expression of Rheb, which activates mTOR activity independently of AKT."
21331300
sparser
"Rheb activates mTOR, while the TSC1/TSC2 complex, by inhibiting Rheb, avidly inhibits mTOR and therefore prevents protein synthesis."
20663687
reach
"TSC1 functions together with TSC2 as an inhibitor of mTOR by maintaining the mTOR activator RHEB in an inactive state."
21533174
reach
"Hamartin and tuberin are involved in the regulation of cell proliferation and differentiation, forming a physical and functional complex that activates GTPase, keeping the protein Ras homolog enriched in brain protein (RHEB) inactive in order to inhibit the mammalian target of rapamycin (mTOR) pathway."
23730262
sparser
"Thus, while these CAAX modifications are necessary for proper subcellular localization, Rheb activation of mTOR is not impaired in the absence of Rce1 or Icmt function."
19838215
sparser
"The Rheb activates mTOR by antagonizing its endogenous inhibitor FKBP38 ( xref )."
19336571
reach
"Ectopic expression of Rheb in PC-3 cells resulted in activation of mTOR as evidenced by about 3.1-fold increase in T389 phosphorylation of its downstream target p70s6k (supplemental Fig."
19336571
reach
"Through the small G protein Rheb, the TSC proteins, hamartin and tuberin, negatively regulate mammalian target of rapamycin complex 1 (mTORC1) signaling."
23514105
sparser
"Rheb-GTP can activate mTOR through direct interaction with it ( xref ; xref )."
25358358
sparser
"Since it remained possible that FTS may disrupt Rheb interaction with mTOR, we next asked if FTS inhibits Rheb-induced activation of mTOR."
19838215
reach
"Rheb activation of mTOR is more dependent on farnesylation than on postprenylation CAAX processing."
19838215
reach
"Overexpression of Rheb Induces mTOR Signaling through a PI3K independent Mechanism in Skeletal Muscle Myoblasts."
20668162
sparser
"Rheb, in its GTP-bound state, can activate mTOR."
16404421
reach
"We found that Rheb expression significantly enhanced mTOR activity, as determined by increased phosphorylation of p70 S6 (XREF_FIG)."
22145042
sparser
"Additionally, PLD1, but not PLD2, was shown to be required for the activation of mTOR by Rheb [ xref ]."
20399893
sparser
"The tuberous sclerosis complex (TSC) includes TSC2, a GAP inactivating the GTPase Rheb ( xref ; xref ), which in turn activates mTOR ( xref ; xref )."
29625033
reach
"The TSC1 and TSC2 gene products form a functional complex that has GTPase activating protein (GAP) activity toward Ras homolog enriched in brain (Rheb) to inhibit mammalian target of rapamycin complex 1 (mTORC1), which is constitutively activated in TSC mutant tumors."
20616807
sparser
"Akt phosphorylation inactivates the tuberous sclerosis complex (TSC) formed by hamartin (TSC1) and tuberin (TSC2; xref ), leading to accumulation of the GTP-bound form of the small G protein Rheb that activates mTOR ( xref )."
17646396
sparser
"Uninhibited Rheb then activates mTOR, which then regulates three key components involved in translation initiation: eIF4E, eIF4G, and S6 kinase (S6K) [ xref , xref – xref ]."
26269784
reach
"Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38, though this remains controversial."
20528734
trips
"Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38."
17991864
sparser
"Tuberin/hamartin complex has also strong and highly specific GAP activity toward Rheb (Ras homolog enriched in brains), which activate mammalian target of rapamycin (mTOR) ."
17376623
reach
"TSC1 and TSC2 form a complex that inhibits Rheb directed mTOR activation through a GTPase activating protein (GAP) domain in the TSC2 C terminus."
27795403
reach
"AMPK can induce autophagy by acting via two different pathways, directly, by phosphorylating the proautophagic factor ULK1 [XREF_BIBR, XREF_BIBR], and indirectly, by negatively regulating the mTOR complex targeting them TOR inhibitors tuberous sclerosis complex 1 and 2 (TSC1/2) and the mTOR activator Rheb, a Ras homologue GTP binding protein enriched in the brain [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
28055974
reach
"Whether TSC1/2 and/or Rheb binds to the mTOR complex containing raptor and modulates the signaling function and kinase activity of mTOR remains an important but unanswered question."
14684181
sparser
"This explains why overexpressed Rheb activates mTOR in the absence of amino acids; presumably the Rheb-mTOR interaction is driven by mass action in this case, and no longer requires the amino acid–stimulated movement of mTOR to late endosomes."
20053679
reach
"In contrast, although Rce and Icmt were required for proper Rheb localization, neither of the post-prenyl processing steps was required for Rheb induced mTOR activation."
19838215
sparser
"In summary, we have found that inhibition of Rce1- and Icmt-catalyzed modifications does not prevent Rheb activation of mTOR, and that FTS inhibits mTOR through a mechanism that does not involve Rheb inhibition."
19838215
reach
"Therefore, Rheb overexpression supersedes the dependency of the nutrient input to mTOR, suggesting that Rheb is an activator of mTOR within the nutrient signaling pathway."
12906785
sparser
"In another model, Sun et al. ( xref ) suggested that phospholipase D1 (PLD1) plays a key role in the Rheb-induced activation of mTOR1."
21196241
sparser
"Phosphorylation activation of TSC1/2 activates autophagy by interfering with GTPase Rheb activity, which avoids mTOR activation by GTPase Rheb, thus inhibiting mTOR activity (Huang and Manning, xref )."
29018776
reach
"To determine whether the Rheb induced mTOR signaling through a PI3K dependent mechanism, the PI3K inhibitor wortmannin was used."
20668162
sparser
"MTOR is activated by the small guanosine triphosphatase (GTPase) Ras homolog enriched in brain (Rheb)( xref , xref ), which is the target of the GTPase-activating domain of the tuberous sclerosis complex 2 (TSC2) protein."
24398473
reach
"Rheb activates mTOR pathway in 293T cells and DRG."
27264357
reach
"On the other hand, ATF6 activation is crucial to long-term survival of tumors by augmenting resistance to chemotherapy, nutrient starvation and stress in quiescent squamous carcinoma cells, where ATF6 increases Rheb expression, which in turn activates mTOR activity in an Akt independent manner."
23317820
reach
"Rheb activates mTOR by antagonizing its endogenous inhibitor, FK506 binding protein 38 (FKBP38) [XREF_BIBR], though this remains controversial [XREF_BIBR]."
23272914
sparser
"MTOR is activated by the small GTP binding protein, Rheb, whose GTPase activity is under negative control by the TSC1/2 dimer."
20005690
reach
"In particular, the activation of mTOR by Rheb is not well known but future studies may shed light on this situation (Inoki et al., 2003)."
26341051
sparser
"Under nutrient-rich conditions, mTOR is mainly activated through a signaling cascade involving activation of class I phosphinositol 3 kinase (PI3K)/protein kinase B (Akt), phosphorylation of tuberous sclerosis complex 2 (TSC2), and activation of the GTP-binding protein Rheb which in turn activates mTOR [ xref ]."
24984281
reach
"Both Rheb1 and Rheb2 transgenes can activate mTor in heterologous cells."
21238928
sparser
"Neither Htt knockdown nor Htt overexpression showed any obvious effect on mTOR kinase activity when assessed by the phosphorylation of the downstream mTOR effector S6K at Thr389 xref under basal conditions or upon activation of mTOR by the upstream regulator Rheb ( xref )."
25686248
sparser
"Collectively, these in vitro studies demonstrate a link between two pathways that regulate mTOR, PLD/PA and TSC2/Rheb, and provide further insight into a mechanism by which Rheb activates mTOR."
19166931
sparser
"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."
28319048
sparser
"Furthermore, Tsc2 deficiency and hyperactive Rheb constitutively activate mTOR and inhibit ephrin-induced growth cone collapse."
20062052
reach
"It therefore seems possible that WSSV might likewise express one or more viral proteins that functionally replace the mTOR activator Rheb or otherwise activate the mTOR pathway."
24945378
sparser
"Akt1-3 activity fosters the inhibition of the tuberous sclerosis proteins 1 and 2 (TSC1 and TSC2), and TSC1/2 inhibition, in turn, facilitates Rheb small GTPase-mediated activation of mTOR."
33765445
reach
"[XREF_BIBR] This led us to propose that RHEB normally contacts and activates lysosome localized mTOR from a distinct endomembrane compartment (XREF_FIG) (a relationship which we termed " transendomembrane " to contrast to the prevailing " cis-" interaction in which both RHEB and mTOR are proposed to both be lysosomal)."
31157925
reach
"In the normal state, the hamartin and tuberin complex activates the protein Ras homolog enriched in brain (Rheb), which inhibits mammalian target of rapamycin (mTOR)."
21949518
reach
"When in its GTP state, Rheb is a potent activator of mTOR."
15318929
reach
"Rheb binds directly to the amino-terminal lobe of the mTOR catalytic domain, and activates mTOR kinase in a GTP dependent manner."
15878852
reach
"To determine whether Rheb could induce activation of mTOR in DRG neurons, we transduced cultured adult DRG neurons using wtRheb-lentivirus."
27264357
reach
"AKT promotes activation of the Rheb small GTPase, which then activates mTOR, a protein that is involved in growth factor signaling, the energy state of the cell, and nutrient and oxygen availability."
27096871
sparser
"Activated Rheb activates mTOR to inhibit autophagy (see xref ) [ xref , xref – xref ]."
33628363
sparser
"RheB activates the mechanistic target of rapamycin (mTOR), a serine/threonine kinase involved in the formation of two complexes, mTORC1 and mTORC2 ( xref )."
29163356
reach
"Rheb is an activator of mTOR."
21210909
reach
"Furthermore, the intracellular levels of free Mg 2+ might play a crucial role in the regulation of the activities of the principal mTOR modulators such as Rheb and Rag GTPases [XREF_BIBR - XREF_BIBR]."
29435164
reach
"MTOR can be activated by RHEB either on the surface of the peroxisome [XREF_BIBR]-in response to reactive oxygen species (ROS)-or on the surface the lysosome [XREF_BIBR]-in response to amino acids."
29570707
reach
"By contrast, the interaction of NIX with Rheb elicited mTOR independent effects on cell growth [XREF_BIBR]."
25810907
reach
"In other studies, conditional expression of the mTOR activator Rheb (a downstream effector of Akt) in neural progenitors has been shown to promote myelination in the brain, while conditional Rheb knockout from the same cells inhibits myelination [XREF_BIBR]."
23558589
reach
"To further study the mechanisms of epileptogenesis and hyperexcitability in mTORopathies vs GATORopathies, a plasmid encoding a constitutively active form of the mTOR activator Rheb was introduced to the fetal mouse brain by in utero electroporation."
31625153
sparser
"Rheb activates the mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cellular growth and metabolism in the Ras/PI3K/Akt/mTOR pathway."
33440168
reach
"When the TSC complex is inhibited by AKT, RHEB activates mTOR [XREF_BIBR]."
27860216
sparser
"It has recently been shown that Rheb activates mTOR by binding to its endogenous inhibitor FKBP38 and preventing it from association with mTOR."
18658153
reach
"Ras homolog enriched in brain (Rheb) is a direct activator of mTOR and was shown to activate the mTOR pathway in many studies."
27264357
reach
"AMPK has been shown to inhibit mTORC1 activity by two different mechanisms : one through activation of the TSC2, which promotes downstream inhibition of the mTOR activator Rheb [XREF_BIBR, XREF_BIBR], and the other through direct phosphorylation of Raptor at Ser792 blocking mTORC1 activation [XREF_BIBR]."
20863384
reach
"It has recently been shown that Rheb activates mTOR by binding to its endogenous inhibitor FKBP38 and preventing it from association with mTOR."
18658153
reach
"Thus, the lack of an effect of Rheb on PKB (308) phosphorylation suggests that, similar to the results obtained in C2C12 myoblasts, overexpression of Rheb induces mTOR signaling through a PI3K independent mechanism in adult skeletal muscle in vivo."
20668162
reach
"AAV mediated transduction of SN dopamine neurons with constitutively active forms of the kinase Akt or the GTPase Rheb, both of which stimulate mTor activity, induces long-range growth that reaches striatal target and restores function."
26192625
reach
"Here, we find that PLD1, but not PLD2, is required for Rheb activation of the mTOR pathway, as demonstrated by the effects of RNAi."
18550814
sparser
"Diabetes increases mTOR activity in the kidney, probably due to reduced AMP-activated protein kinase signaling [ xref ] or decreased interaction between glyceraldehyde 3-phosphate dehydrogenase and Rheb [ xref ], each of which promotes mTOR activation by Rheb [ xref ]."
35054991
sparser
"It is well described that RHEB activates mTOR kinase, which in turn phosphorylates 4EBP1 and S6K and finally stimulates protein synthesis."
30558189
reach
"These observations were not unique to the MDA-MB-231 cell line because Rheb mediated activation of mTOR failed to confer any protection against BITC induced autophagy or growth inhibition in the MCF-7 cell line (results not shown)."
22457718
sparser
"Furthermore, the upregulation of mTOR activation by high expressed Rheb increased the level of glycolytic metabolism and cell viability inhibited by DHA."
25799586
reach
"We also report that Tuberin-Hamartin heterodimers inhibit Rheb induced mTOR signaling, which requires an intact GAP domain of Tuberin."
12906785
sparser
"This process activates the serine-threonine kinase Akt, which phosphorylates tuberous sclerosis complex 2 (TSC-2) and decreases the inhibition of Rheb, which activates mTOR ( xref )."
31178754
reach
"Ectopic expression of Rheb in MDA-MB-231 cells resulted in activation of mTOR as evidenced by about 4.9-fold increase in T389 phosphorylation of P70s6k (XREF_FIG)."
22457718
sparser
"Active GTP-bound Rheb activates mTOR, but TSC1/TSC2 activity results in GDP-loaded Rheb and in loss of mTOR activation leading to dephosphorylation of the mTOR effectors S6K (ribosomal protein kinase)[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17010524
reach
"The Rheb mediated activation of mTOR conferred marginal protection against PEITC mediated cleavage of LC3."
19336571
sparser
"Instead, we found that FTS blocked Rheb activation of mTOR, but this effect was independent of inhibition of Rheb or of any other prenylated protein."
19838215
reach
"To our surprise, Rheb mediated activation of mTOR fails to confer any protection against cell killing or apoptotic DNA fragmentation by BITC (Singh SV, unpublished observations) in either MDA-MB-231 or MCF-7 cells."
22457718
reach
"Striatal levels of Rheb, which also activates mTOR, are unaltered in Rhes deleted striatum (XREF_SUPPLEMENTARY)."
22179112
reach
"Rheb (Ras homolog enriched in brain), a GTP binding protein, is a key activator of mTOR and is inhibited by Rheb-GTPase-activating protein (GAP)."
22279066
reach
"Though Rheb is well known to activate mTOR, the physiologic rationale for this action has not been altogether clear."
25660019
sparser
"To confirm the regulation role of mTOR in G9a inhibition induced autophagy, we next overexpressed Rheb, which intensively activates mTOR in TCC T24 and UMUC-3[ xref ]."
26397365
reach
"Recently, it has been reported that GAPDH competes with mammalian target of rapamycin (mTOR) for binding to the mTOR activator Rheb and prevents mTOR activation under low-glucose conditions (Lee et al[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26626483
reach
"Rheb activates mTOR, while the TSC1 and TSC2 complex, by inhibiting Rheb, avidly inhibits mTOR and therefore prevents protein synthesis."
20663687
reach
"Hamartin and tuberin are involved in the regulation of cell proliferation and differentiation, forming a physical and functional complex that activates guanosine triphosphatase (GTPase), keeping the protein Ras homolog enriched in brain protein (RHEB) inactive in order to inhibit the mammalian target of rapamycin (mTOR) pathway."
24044547
sparser
"Rheb-GTP conformationally activates mTORC-1, which phosphorylates its downstream effectors 4E-BP1 and S6 kinases ( xref )."
24604594
reach
"Siah1 degrades Rheb leading to reduced mTOR signaling, while ketamine, conversely, stabilizes Rheb that enhances mTOR signaling."
26782056
reach
"Skeletal muscle overexpression of Rheb increased mTOR mediated kinase events resulting in increased skeletal muscle size and protein translation independent of PI3-kinase and PKB (AKT) [XREF_BIBR]."
24053798
reach
"RHEB GTP activates mTOR (mammalian target of rapamycin)."
24710490
sparser
"One of the major effects of the activation of mTOR by Rheb is to suppress autophagy [ xref ]."
27034171
sparser
"Rheb interacts directly with mTOR and activates mTOR kinase ( xref ), whereas Rabin8 interacts with Rheb and inhibits the phosphorylation of Ser235/Ser236 in small ribosomal subunit protein S6 ( xref )."
25358358
reach
"Akt1, in turn, activates mTORC1 by inhibiting the GAP TSC1/2 complex, thus activating the GTPase Rheb, which activates mTOR."
20495773
reach
"This complex connects downstream with the Ras related GTPase Rheb; when TSC1/2 is suppressed, Rheb stimulates the activity of mTOR and when TSC1/2 is active, turns the GTP bound form of Rheb into its [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20207176
reach
"While Rce1- and Icmt catalyzed modifications were required for proper Rheb localization, surprisingly, they were dispensable for Rheb mediated activation of mTOR."
19838215
eidos
"It was unveiled that circMYLK sponged miR-1301-3p to promote RHEB expression , which resulted in mTOR signaling activation and CC cell malignant growth ."
32547198
reach
"There is evidence indicating that BNIP3 inhibits the mTOR pathway through RHEB (an activator of mTOR) [50], and this protein has been shown to induce cell death by autophagy which was inhibibed by 3-M[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24511615
reach
"In addition to its potential direct activation of mTOR, Rheb may indirectly stimulate mTOR through its ability to bind and activate phospholipase D (PLD)."
19302577
reach
"Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38."
17991864
reach
"To determine whether the overexpression of Rheb could induce mTOR signaling in adult skeletal muscle in vivo, mouse TA muscles were transfected with Rheb, or GFP as a control condition, and the phosphorylation of the ribosomal S6 (S6) protein on the Ser235/236 residues (P-S6) was evaluated as a marker of mTOR signaling."
20668162
reach
"Additionally, AKT phosphorylates and activates the mTOR protein kinase by circumventing the inhibitory GTPase activity of the TSC2 tumor suppressor, tuberin, for the small G protein, Rheb, which binds directly to the kinase domain and activates mTOR in a GTP dependent manner [XREF_BIBR - XREF_BIBR]."
19450179
reach
"The mTOR activator Rheb (ras homolog enriched in brain), which is directly suppressed by the TSC1/2 complex, is activated by SynGAP following NMDAR stimulation [36], so the reduction of SynGAP may be a homeostatic response to chronically activated Rheb."
30237867
sparser
"Our mechanistic studies demonstrate that the inhibition of PPT1 initiates a cascade, beginning with the lysosomal displacement of vATPase subunits, which disrupts the function of Ragulator and Rag GTPase machinery, impairing lysosomal recruitment of mTORC1, and preventing Rheb-dependent activation of mTOR."
28899863