IndraLab
Statements
reach
"Western blot studies showed that the expression and activation of mTOR were both inhibited by GL-V9 (XREF_FIG E), because mTOR specifically phosphorylates the p70S6 kinase at Thr 389, the phosphorylation of p70S6 kinase at this position is a routine and specific assay for monitoring mTOR activity [XREF_BIBR]."
reach
"Further downstream, mTOR phosphorylates p70 S6 kinase (T389), a regulator of Ribosomal Protein S6 (RPS6) responsible for mRNA translation, and has been proposed to signal via 14-3-3 (tyrosine 3-monooxygenase), a required protein in Raf signaling, to inhibit IRS-1 in a negative feedback loop XREF_BIBR."
"We report here that a mammalian recombinant p70alpha polypeptide, extracted in an inactive form from rapamycin-treated cells, can be directly phosphorylated by the mTOR kinase in vitro predominantly at the rapamycin-sensitive site Thr-412. mTOR-catalyzed p70alpha phosphorylation in vitro is accompanied by a substantial restoration in p70alpha kinase activity toward its physiologic substrate"
reach
"The site at Thr389 is essential to the function of S6K1, and activated mTOR can phosphorylate S6K1 at the Thr389 residue, causing phosphorylation and recruitment of the 40S ribosomal unit and finally enhancing the translation of mRNAs, including elongation factors and ribosomal proteins XREF_BIBR."
rlimsp
"This proposal is not supported, however, by the existence of mutants of S6K1 that are phosphorylated in vivo on Thr(389) in a rapamycin-resistant fashion. Here, we demonstrate that the raptor-mTOR complex phosphorylates the rapamycin-sensitive forms of S6K1, while the distinct rictor-mTOR complex phosphorylates the rapamycin-resistant mutants of S6K1. Phosphorylation of Thr(389) by rictor-mTOR is independent of the TOR signaling motif and depends on removal of the carboxyl terminal domain of S6K1."
rlimsp
"We then immunopurified HA-S6K1 after inhibitor and EGF stimulation and incubated them with immunopurified myc-mTOR to see whether mTOR can phosphorylate S6K1 at Thr-389 in the absence of Thr-229 phosphorylation by PDK1. As shown in Fig. 5b, only pretreatment with PDK1 leads to phosphorylation of Thr-389 by mTOR, suggesting that Thr-389 is followed by Thr-229."
rlimsp
"We found that the effects of rapamycin were specific to inhibition of mTOR/p70S6K, since rapamycin treatment had no significant effect of phospho-ACC levels (Fig. 5A), indicating no effect on AMPK activity, but, rather, significantly inhibited phosphorylation of p70S6K on Thr 389 (Fig. 5B), which is the mTOR phosphorylation site critical for kinase function (Saitoh et al., 2002)."
sparser
"Western blot studies showed that the expression and activation of mTOR were both inhibited by GL-V9 ( xref E), because mTOR specifically phosphorylates the p70S6 kinase at Thr-389, the phosphorylation of p70S6 kinase at this position is a routine and specific assay for monitoring mTOR activity [ xref ]."
rlimsp
"In this context, activation of mTORC1 leads to increased translation and cell growth by two mechanisms: first, phosphorylation of Thr389 of S6K1 by mTOR results in activation of S6K1 and subsequent phosphorylation of five evolutionarily conserved residues (Ser235, Ser236, Ser240, Ser244, and Ser247) of ribosomal protein S6 (RPS6) that activates RPS6."
reach
"In this context, activation of mTORC1 leads to increased translation and cell growth by two mechanisms : first, phosphorylation of Thr 389 of S6K1 by mTOR results in activation of S6K1 and subsequent phosphorylation of five evolutionarily conserved residues (Ser235, Ser236, Ser240, Ser244, and Ser247) of ribosomal protein S6 (RPS6) that activates RPS6."
sparser
"PHD3 knockdown also increased the phosphorylation of JNK at Thr 183 and Tyr 185 under basal and TNF-α-stimulated conditions (Fig. xref ) but reduced mTOR complex 1-dependent phosphorylation of p70 S6 kinase at Thr 389 , Thr 421 , and Ser 424 (ref. xref ) under insulin stimulation (Supplementary Fig. xref ), consistent with impaired insulin signalling."
rlimsp
"The site at Thr389 is essential to the function of S6K1, and activated mTOR can phosphorylate S6K1 at the Thr389 residue, causing phosphorylation and recruitment of the 40S ribosomal unit and finally enhancing the translation of mRNAs, including elongation factors and ribosomal proteins [31]."
rlimsp
"As phosphorylation of Thr(389) is rapamycin sensitive and mTOR can phosphorylate the same site in vitro, it has been suggested that mTOR is the physiological Thr(389) kinase. This proposal is not supported, however, by the existence of mutants of S6K1 that are phosphorylated in vivo on Thr(389) in a rapamycin-resistant fashion."