IndraLab

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AKT1S1 activates MTOR. 10 / 34
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"The induced phosphorylation of PRAS40 has been posited to increase mTOR activity [XREF_BIBR; XREF_BIBR]."

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"Furthermore, PRAS40 phosphorylation by Akt and association with 14-3-3, a cytosolic anchor protein, are crucial for insulin to stimulate mTOR."

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"When viewed in this light, our results suggest that phosphorylation of PRAS40 at T246 may not be essential, or at least not sufficient to positively regulate mTOR activity and protein synthesis."

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"For instance, protein levels of p-P70S6K and p-S6 in the mTOR pathway were shown to be decreased in PRAS40 KO mice (XREF_FIG), but these two proteins were not examined in PRAS40 transfected brains, even though we have shown that PRAS40 vector transfection promoted mTOR activity (XREF_FIG)."

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"PRAS40 knockdown could inhibit the activities of the mTOR pathway; moreover, neuronal autophagy and apoptosis were exacerbated by PRAS40 knockdown."

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"Binding of PRAS40 to the mTORC1 signaling complex attenuates mTOR ac-tivity, presumably by inhibition of downstream substrate binding; however, phosphorylation of the Thr246 residue by Akt and PKB rel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"XREF_BIBR, XREF_BIBR Nevertheless, considerable evidence exists to show that insulin can enhance the activation of mTOR via stimulation of 4EBP1 binding to dimeric mTOR complex 1, XREF_BIBR and mediated by the Akt and PKB substrate PRAS40 (proline rich Akt and PKB substrate 40 kDa)."

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"Both kinases phosphorylate proline rich-AKT substrate 40 (PRAS40), which increases mTOR kinase activity on dissociation from mTORC1."

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"Intriguingly, while the levels of p-AKT (serine 473) remained unchanged, the levels of p-GSK3beta, p-PRAS40 and p-AKT substrates increased markedly in L-Atg5 and mTOR DKO livers (XREF_FIG)."

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"Given these data and the role of PRAS40 in insulin signaling, it is tempting to speculate that Abeta accumulation increases PRAS40 phosphorylation, which in turn leads to chronic hyperactive mTOR and [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
AKT1S1 bound to p14_3_3 activates MTOR. 1 / 1
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"Under normal growth conditions, 14-3-3 protein binding to TSC2 and PRAS40 leads to mTOR activation."
AKT1S1 activates phosphorylated MTOR. 1 / 1
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"The results showed that PRAS40 knockdown reduced p-mTOR expression , whereas the expression of p-RSK did not change following PRAS40 knockdown ( Figure S1B ) ."
AKT1S1 phosphorylated on T246 activates MTOR. 1 / 1
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"Furthermore, PRAS40 phosphorylation by Akt and association with 14-3-3, a cytosolic anchor protein, are crucial for insulin to stimulate mTOR. -- (From Results Section) Because insulin stimulates Akt-mediated phosphorylation of PRAS40 at Thr 246 (ref. 26), we considered the possibility that PRAS40 phosphorylation may influence insulin activation of mTOR. Both wild-type PRAS40 and mutant PRAS40T246A expressed in 293T cells inhibited S6K1 phosphorylation and this inhibition was reduced on Akt1 coexpression with wild-type PRAS40 but not PRAS40T246A--"
Phosphorylated AKT1S1 activates MTOR. 1 / 1
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"As a result, phosphorylated PRAS40 binds to the docking protein 14-3-3 to inhibit PRAS40 and activate mTOR signaling."