IndraLab

Statements

TSC1 bound to TSC2 inhibits MTOR. 51 / 51
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"TSC2 forms a heterodimeric complex with TSC1 and negatively regulates mTOR."
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"The TSC1 and TSC2 complex inactivates Rheb to inhibit mTOR signaling XREF_BIBR, XREF_BIBR."
20169165
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"TSC1 and TSC2 complex inhibits mTOR activity by activating the GTPase activity of Rheb, and both Akt and AMPK converged at TSC1 and TSC2 to regulate mTOR activity."
18790744
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"Activation of the TSC1 and TSC2 complex by AMPK can negatively regulate the mTOR pathway not only by inhibiting mTOR activation via Rheb, a member of the Ras family of GTPases, but also by mediating phosphorylation of the mTORC1 partner Raptor."
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"The TSC1 and TSC2 complex inactivates Rheb to inhibit mTOR signaling."
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"As the hamartin and tuberin complex normally inhibits the mTOR pathway, mutation of either TSC1 or TSC2 leads to abnormal disinhibition of the mTOR pathway."
23620711
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"Akt mediated phosphory lation of TSC2 disrupts the TSC1 and TSC2 complex, allowing unrestrained mTOR kinase activity."
14667501
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"The proteins hamartin and tuberin, respectively, encoded by the TSC1 and TSC2 genes, form a complex that downregulates the mTOR pathway."
29167182
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"We may add that activated AMPK is also known to downregulate the mTOR-p70S6K-S6 ribosomal protein phosphorylation cascade by phosphorylating TSC2 and increasing the activity of the TSC1 and TSC2 compl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Overexpression of constitutively activated Akt or disruption of TSC1 and TSC2 complex by small interfering RNA or gene knockout only partially restored curcumin mediated inhibition of mTOR and downstream signaling, indicating that they are not the primary effectors of curcumin mediated inhibition of Akt and mTOR signaling."
18790744
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"These results indicate that TBC7 localizes in the cytoplasmic vesicles of the endomembrane in association with the TSC1-TSC2 complex.The role of TBC7 was investigated in the association with the TSC1 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Rheb activates mTOR, while the TSC1 and TSC2 complex, by inhibiting Rheb, avidly inhibits mTOR and therefore prevents protein synthesis."
20663687
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"LKB1 phosphorylates AMPK, which subsequently targets the TSC1 and TSC2 complex that then inhibits mTOR."
20460169
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"The TSC1 and TSC2 proteins form a heterodimer that negatively regulates the mTOR pathway, which in turn modulates a wide array of cellular processes (Hay, 2004)."
23664552
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"The TSC1 and TSC2 complex inhibits mTOR signaling, and the phosphorylation of TSC2 reverses this inhibition."
| PMC
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"The TSC1 and TSC2 complex promotes stabilization of Rheb-GDP, and consequent inhibition of mTOR activity."
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"LKB1 phosphorylates AMPK which subsequently targets the TSC1 and TSC2 complex that then inhibits the mammalian target of rapamycin (mTOR)."
19931409
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"MTOR is downregulated by the upstream TSC1 and TSC2 complex."
20169165
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"TSC2 is phosphorylated and inactivated by Akt and the TSC1 and TSC2 complex negatively regulates the kinase mTOR."
29462936
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"Their protein products, hamartin and tuberin, respectively, form a dimer that acts via the GAP protein Rheb (Ras homolog enhanced in brain) to directly inhibit mTOR, again resulting in upregulation."
22544507
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"Since the TSC1 and TSC2 complex negatively regulates mTOR activity, the enlarged neurons of cortical tubers have high mTOR activity as measured by increased ribosomal protein S6 phosphorylation."
23485365
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"Hamartin and tuberin, the TSC1 and TSC2 gene products, form a complex that inhibits mammalian target of rapamycin (mTOR) in a conserved cellular signaling pathway (PI3kinase- Akt-mTOR pathway) that regulates nutrient uptake, growth and protein translation [9], [10], [11]."
21915260
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"TSC1 and TSC2 complex inhibits mTOR activity and restrains cell growth by stimulating Rheb GTP hydrolysis [24]."
18036779
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"GTP bound RHEB is known to activate mTOR, whereas GDP bound RHEB loses its ability to activate mTOR, suggesting that the TSC1 and TSC2 complex can downregulate the mTOR pathway through suppressing RHE[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17693255
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"When present as a heterodimer the TSC1 and TSC2 complex inhibits mTOR indirectly by converting the small GTPase Ras homolog enriched in brain (Rheb) to an inactive GDP bound form."
19795384
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"Recent studies suggested that TSC2 functions as the GTPase activating protein of the small G protein Rheb, an upstream activator of mTOR, and that the TSC1 and TSC2 complex antagonizes the mTOR signaling pathway via stimulation of GTP hydrolysis of Rheb."
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"Thus, TSC1 and TSC2 complex is more available to inhibit the mTOR pathway, demonstrated for the first time in rat primary neuronal cultures."
19631745
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"Inactivation of the TSC1 and TSC2 complex stimulates activity of mammalian target of rapamycin (mTOR), a kinase that promotes the uptake of nutrients necessary for cellular growth."
21876842
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"The TSC-1/TSC-2 protein complex (Plank et al., 1998; van Slegtenhorst et al., 1998) negatively regulates the mammalian target of rapamycin (mTOR) pathway, which is triggered by growth factors as well as nutrients and regulates protein synthesis, autophagy, transcription cell growth, cell proliferation, cell motility (Hay and Sonenberg, 2004; Sarbassov et al., 2005)."
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"Once activated, the TSC1 and TSC2 complex inhibits mTOR resulting in a decrease in protein synthesis."
19308685
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"In particular, hamartin and tuberin, proteins encoded by the TSC1 and TSC2 genes, form a complex that normally inhibits the mTOR pathway via inhibition of the intermediary GTP binding protein Rheb."
23620711
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"As the hamartin and tuberin complex normally inhibits the mTOR pathway, mutation of either TSC1 or TSC2 leads to abnormal disinhibition of the mTOR pathway."
23644232
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"According to a model based on these data, in the absence of growth factors the TSC1 and TSC2 complex is hypophosphorylated and inhibits mTOR."
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"AMPK is activated by the phosphorylation of T172, which is regulated by LKB1 (56), and increased LKB1/AMPK signaling activates the TSC1/TSC2 complex, which, in turn, inhibits mTOR activity (38) ."
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"Most TSC patients present with mutations in the TSC1 or TSC2 genes, which encode proteins that form the TSC1-TSC2 complex that serves to antagonize the signaling pathway downstream of mammalian target of rapamycin (mTOR) by promoting the activation of the small GTPase Rheb and thereby inhibiting cellular growth and proliferation."
34901059
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"Hamartin and tuberin, proteins encoded by the tuberous sclerosis complex 1 and 2 genes, form a complex that normally inhibits the mTOR pathway via inhibition of the intermediary GTP binding protein Rheb (Ras homolog enriched in brain)."
23644232
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"The mTOR is negatively regulated by TSC1 and TSC2 complex."
23389114
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"These two proteins bind to each other, via their respective coiled-coil domains, to form an intracellular hamartin-tuberin complex that negatively regulates the Mammalian Target of Rapamycin Complex 1 (mTORC1) signaling, which is a major regulator of anabolic cell growth."
| PMC
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"Hamartin and tuberin form a heterodimer to inhibit mTOR kinase through Ras homologue enriched in brain (Rheb) suppression."
24662006
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"Tuberous sclerosis complex 1 (TSC1) and TSC2 form a heterodimer that negatively regulates mTOR, preventing the phosphorylation of S6K."
20054236
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"Previous literature has shown that increased LKB1/AMPK signaling also activates the TSC1/TSC2 complex, which, in turn, inhibits mTOR activity (38) ."
35263141
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"TSC1 (hamartin) forms a complex with TSC2 (tuberin) that negatively regulates mTOR through Rheb inhibition, thus Tsc1 loss results in increased mTORC1 activity (XREF_FIG)."
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"This activation of PI3K results in a cascade of phosphorylation events, resulting in the activation of Akt, which in turn inhibits the TSC1 and TSC2 complex, which negatively regulates mTOR by acting as a GTPase activating protein toward Ras homolog enriched in brain (Rheb), a direct and positive regulator of mTOR."
28288694
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"These findings strongly implicate the tuberin-hamartin tumor suppressor complex as an inhibitor of mtor"
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"Activation of TSC1/TSC2 complex decreases MTOR activity by inhibiting RHEB, a positive MTOR regulator."
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"The TSC1 and TSC2 complex is often inhibited under growth conditions to facilitate mTOR activation."
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"Moreover, adiponectin is able to up-regulate phosphorylation of AMPK, promoting TSC1/TSC2 complex formation, which in turn inhibits mTOR activation, and thus ERα-negative cell growth (52)."
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"The TSC1 and TSC2 complex persistently activates the mammalian target of rapamycin (mTOR) signaling pathway, which regulates cellular metabolism, growth and survival."
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"Upon activation, AKT not only activates mTOR signaling by direct phosphorylation at Ser2448 of mTOR but also catalyzes phosphorylation at Thr1462 of TSC2 that inhibits TSC1/TSC2 complexes, a master negative regulator of mTOR (148, 149)."
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"Recently, it has been shown that TSC1 and TSC2 form a complex that inactivates mTOR and so inhibits the activity of S6K [68]."
12946627
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"AKT represses the ability of the TSC1/TSC2 complex to inhibit activation of mTOR, and these two genes are most frequently found to be mutated in TSC."
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