| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.68182718 |
| Signaling through mTOR is also controlled by upstream members of the pathway such as the Ras homolog enriched in brain ( Rheb ) , a GTPase that activates mTOR , and tuberin ( also known as TSC 2 ) , a GTPase activating protein , which , with its binding partner hamartin ( also known as TSC 1 ) , acts to repress mTOR . 0.68182718^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.80650237 |
| RESULTS : Here , we show that Rheb binds to the TOR complex specifically , independently of its ability to bind TSC 2 , through separate interactions with the mTOR catalytic domain and with LST 8 . 0.80650237^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.8119124 |
| Failure of Rheb to localize to the endomembrane impairs its ability to interact with mTOR and activate downstream targets . 0.8119124^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Rheb has a dual role : it activates mTOR and inactivates B Raf . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| RESULTS : We show that the small G protein Rheb ( Ras homolog enriched in brain ) is a molecular target of TSC1 / TSC2 that regulates mTOR signaling . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| It has recently been shown that TSC 2 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 . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Follicle stimulating hormone activation of hypoxia inducible factor 1 by the phosphatidylinositol 3 kinase / AKT / Ras homolog enriched in brain ( Rheb ) / mammalian target of rapamycin ( mTOR ) pathway is necessary for induction of select protein markers of follicular differentiation . ^^^ Our results define a signaling pathway in GCs whereby the inactivating phosphorylation of tuberin downstream of phosphatidylinositol ( PI ) 3 kinase / AKT activity leads to Rheb ( Ras homolog enriched in brain ) and subsequent mTOR ( mammalian target of rapamycin ) activation . mTOR then stimulates translation by phosphorylating p 70 S6 kinase and , consequently , the 40 S ribosomal protein S 6 . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Several recent reports , however , describe the identification of proteins that modulate amino acid signaling through mTOR , that is the tuberous sclerosis complex proteins 1 and 2 and the Ras homolog enriched in brain ( Rheb ) protein . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Over expression of Rheb but not Rap 1 promoted the activation of S 6 kinase in a rapamycin dependent manner , suggesting that Rheb acts upstream of mTOR . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Rheb GTPase is a direct target of TSC 2 GAP activity and regulates mTOR signaling . ^^^ This function of Rheb is blocked by rapamycin and dominant negative mTOR . ^^^ 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 . ^^^ Our data demonstrate that Rheb acts downstream of TSC1 / TSC2 and upstream of mTOR to regulate cell growth . . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Biochemical studies have shown that activated Akt phosphorylates TSC 2 in the TSC1 / TSC2 protein complex , inactivating it ; while TSC1 / TSC2 has GAP activity for the Rheb GTPase ( a member of the ras family ) , and activated Rheb GTP activates mTOR . ^^^ Thus , in cells lacking TSC 1 or TSC 2 there are increased levels of Rheb GTP which leads to activation of mTOR , leading to cell size increase and growth . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| The signaling pathway downstream of Akt leading to mTOR involves the protein products of the genes mutated in tuberous sclerosis , TSC 1 and TSC 2 , and the small guanosine triphosphatase , Rheb . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Further understanding of regulation of the mTOR raptor complex in response to the nutritional environment would require identification of the interplay between the mTOR raptor complex and its upstream effectors such as the protein products of tumor suppressor gene tuberous sclerosis complexes 1 and 2 , and the Ras related small G protein Rheb . . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Recent studies have demonstrated that TSC 2 displays GAP ( GTPase activating protein ) activity specifically towards the small G protein Rheb and inhibits its ability to stimulate the mTOR signaling pathway . ^^^ To investigate the function of TSC 2 and Rheb in mTOR signaling , we analyzed the TSC 2 stimulated Rheb GTPase activity . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Inappropriate activation of the TSC / Rheb / mTOR / S6K cassette induces IRS1 / 2 depletion , insulin resistance , and cell survival deficiencies . ^^^ Loss of function of the TSC 1 TSC2 complex , which acts as a Rheb GAP , yields constitutive , unrestrained signaling from the cell growth machinery comprised of Rheb , mTOR , and S6K . ^^^ We demonstrate herein that constitutive activation of the Rheb / mTOR / S6K cassette , whether by genetic deletion of TSC 1 or TSC 2 or by ectopic expression of Rheb , is sufficient to induce insulin resistance . ^^^ Our results suggest that inappropriate activation of the Rheb / mTOR / S6K pathway imposes a negative feedback program to attenuate IRS dependent processes such as cell survival . . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Hamartin and tuberin , the TSC 1 and TSC 2 gene products , interact and the tuberin hamartin complex inhibits cell growth by antagonising signal transduction to downstream effectors of the mammalian target of rapamycin ( mTOR ) through the small GTPase rheb . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| The mTOR / S6K signalling pathway : the role of the TSC1 / 2 tumour suppressor complex and the proto oncogene Rheb . ^^^ Here we review recent findings demonstrating that the TSC1 / TSC2 inhibitory complex normally acts on Rheb to mediate mTOR / S6K1 signalling . . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| The small GTPase Rheb displays unique biological and biochemical properties different from other small GTPases and functions as an important mediator between the tumor suppressor proteins TSC 1 and TSC 2 and the mammalian target of rapamycin to stimulate cell growth . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| TSC 2 contains a GTPase activator domain that promotes hydrolysis of GTP bound to Rheb , which positively regulates mTOR signaling . ^^^ Although TSC 2 is not required for amino acid control of mTOR , amino acid withdrawal does decrease the proportion of Rheb in the active GTP bound state . ^^^ Here we also show that Rheb and mTOR form stable complexes , which are not , however , disrupted by amino acid withdrawal . ^^^ Mutants of Rheb that can not bind GTP or GDP can interact with mTOR complexes . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Novel role of the small GTPase Rheb : its implication in endocytic pathway independent of the activation of mammalian target of rapamycin . ^^^ Although mammalian target of rapamycin ( mTOR ) kinase is implicated in the downstream target of Rheb , the direct effector ( s ) and exact functions of Rheb have not been fully elucidated . ^^^ The vacuole formation required the GTP form of Rheb , but not the activation of the downstream mTOR kinase . ^^^ These results suggest that Rheb regulates endocytic trafficking pathway independent of the previously identified mTOR pathway . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Rheb binding to mammalian target of rapamycin ( mTOR ) is regulated by amino acid sufficiency . ^^^ Rheb binds directly to the amino terminal lobe of the mTOR catalytic domain , and activates mTOR kinase in a GTP dependent manner . ^^^ Herein we show that the binding of Rheb to endogenous and recombinant mTOR is reversibly inhibited by withdrawal of all extracellular amino acids or just leucine . ^^^ Moreover , the binding of mTOR to Rheb mutants that are unable to bind guanyl nucleotide in vivo is also inhibited by amino withdrawal . ^^^ The inhibitory effect of amino acid withdrawal is exerted through an action on mTOR , at a site largely distinct from that responsible for the binding of Rheb ; deletion of the larger , carboxyl terminal lobe of the mTOR catalytic domain eliminates the inhibitory effect of amino acid withdrawal on Rheb binding , without altering Rheb binding per se . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| REDD 1 likely acts on the TSC1 / 2 complex , as regulation of mTOR substrate phosphorylation by REDD 1 requires TSC 2 and is blocked by overexpression of the TSC1 / 2 downstream target Rheb but is not blocked by inhibition of AMPK . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Rheb ( Ras homologue enriched in brain ) is a farnesylated small GTPase that positively regulates mTOR ( mammalian target of rapamycin ) signaling . ^^^ The farnesyl transferase inhibitor ( FTI ) SCH 66336 ( lonafarnib ) inhibits Rheb farnesylation and mTOR signaling . ^^^ SCH 66336 treatment also inhibited the phosphorylation of S 6 ribosomal protein , a downstream target of Rheb and mTOR signaling . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| The small G protein Rheb ( Ras homologue enriched in brain ) is known to promote mammalian target of rapamycin ( mTOR ) signaling . ^^^ Analysis of mTOR signaling by the small G proteins , Rheb and RhebL 1 . ^^^ In this study , we show that Rheb like 1 protein ( RhebL 1 ) rescues mTOR signaling during nutrient withdrawal and that tuberous sclerosis complex 1 ( TSC ) and TSC 2 impairs RhebL 1 mediated signaling through mTOR . ^^^ We identify critical residues within the switch 1 region ( N 41 ) and ' constitutive ' effector ( Ec ) region ( Y / F54 and L 56 ) of Rheb and RhebL 1 , which are required for their efficient activation of mTOR signaling . ^^^ Mutation of Rheb and RhebL 1 at N 41 impaired their interaction with mTOR , which identifies mTOR as a common downstream target of both Rheb and RhebL1 . . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| TSC 2 is a GTPase activating protein for the small GTPase Ras homologue enriched in brain ( Rheb ) , GTP loading of which activates mTOR by a yet unidentified mechanism . ^^^ Since under these conditions Rheb GTP levels remain high , a second level of amino acid sensing exists , affecting mTOR activity in a Rheb independent fashion . . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Inhibition of Rheb is important for the regulation of mTOR pathway , while mutation of hamartin or tuberin results in uncontrolled cell cycle progression . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Recent work identifying two structurally and functionally distinct mTOR containing multiprotein complexes and TSC1 / 2 , rheb , and AMPK as upstream regulators of mTOR is beginning to reveal how mTOR can sense diverse signals and produce a myriad of responses . . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| TSC1 / TSC2 functions as a GAP towards Rheb , which is a major regulator of the mammalian target of rapamycin ( mTOR ) . ^^^ In the absence of either TSC 1 or TSC 2 , high levels of Rheb GTP lead to constitutive activation of mTOR raptor signaling , thereby leading to enhanced and deregulated protein synthesis and cell growth . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| It has been demonstrated that signal transduction from tuberin to mTOR is mediated by a G protein , Ras homologue enriched in brain ( Rheb ) . ^^^ In normal cells , tuberin having GTPase activating protein properties toward Rheb controls signals of nutrient depletion , hypoxia , or stress , not allowing activation of mTOR and subsequent protein translation and cell proliferation . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| TSC 2 mutations and loss of heterozygosity have been identified in sporadic lymphangioleiomyomatosis associated angiomyolipomas , thus implicating the TSC / Ras homolog enriched in brain ( Rheb ) / mammalian target of Rapamycin ( mTOR ) / p70 S 6 kinase signaling pathway in their pathogenesis . ^^^ We hypothesized that this S 6 hyperphosphorylation could reflect mutational activation of Rheb or Rheb like protein ( RhebL 1 ) , Ras family members which directly activate mTOR . ^^^ These data suggest that activation of the Rheb / mTOR / p70 S 6 kinase pathway is related to the pathogenesis of lymphangioleiomyomatosis associated and sporadic angiomyolipomas lacking TSC1 / TSC2 loss of heterozygosity . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Tsc 1 and Tsc 2 proteins form a complex and serve as a GTPase activating protein ( GAP ) for Rheb , a GTPase regulating a downstream kinase , mTOR . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Hyperactivation of mammalian target of rapamycin ( mTOR ) signaling by a gain of function mutant of the Rheb GTPase . ^^^ The Ras related GTPase Rheb has emerged as a key player downstream of TSC 1 2 in activating signaling to mammalian target of rapamycin ( mTOR ) effectors of cell growth such as S6K and 4E BP 1 . ^^^ Compared with wild type Rheb , S16HRheb is more active at promoting the phosphorylation of the mTOR effectors S6K1 and 4E BP 1 . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| PML physically interacts with mTOR and negatively regulates its association with the small GTPase Rheb by favouring mTOR nuclear accumulation . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Key components of the pathway are the lipid kinase PI 3 K , the small guanosine triphosphate binding protein Rheb , and the protein kinases Akt and mTOR . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| Insulin and amino acid regulation of mTOR signaling and kinase activity through the Rheb GTPase . ^^^ Rheb binds directly to the mTOR catalytic domain , and Rheb GTP enables TORC 1 to attain an active configuration . ^^^ Amino acid depletion inhibits TORC 1 acting predominantly downstream of the TSC complex , by interfering with the ability of Rheb to bind to mTOR . ^^^ |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q15382 and P42345 |
Pubmed |
SVM Score :0.0 |
| NA |
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