IndraLab
Statements
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 ]."
sparser
"Then, mTOR phosphorylates downstream p70S6K1 Thr389 and 4E‐BP1 Thr37/46 to activate the eukaryotic initiation cytokines eIF4B and eIF4E and promote protein synthesis and muscle growth. xref Additionally, there is evidence indicating that neurotrophin 3 impacts protein synthesis and metabolic reorganization in neurogenic muscle by activating the TrkC/AKT/mTORC1 pathway in muscle fibres, as opposed to myoblasts. xref "
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
"Although some authors believe that T389 is the best site phosphorylated by mTOR and the major site with which rapamycin interferes to attenuate p70S6K phosphorylation [47], the T421/S424 sites are more sensitive to rapamycin in human SH-SY5Y neuroblastoma cells pre-treated by zinc [48]."
rlimsp
"In this study, the evaluation of mTOR activation using phosphorylation levels of p70S6K at the T389 site as ‘readout’ might not be completely accurate, because in addition to p70S6K, the main downstream effectors of mTOR also include eIF4E and eEF2. Moreover because of the availability of phospho-antibodies to p70S6K, most data generated for p-p70S6K were obtained with antibodies either to the T389 or the T421/S424 sites of p70S6K. Although some authors believe that T389 is the best site phosphorylated by mTOR and the major site with which rapamycin interferes to attenuate p70S6K phosphorylation [47], the T421/S424 sites are more sensitive to rapamycin in human SH-SY5Y neuroblastoma cells pre-treated by zinc [48]."
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."
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]."
rlimsp
"While p70S6K phosphorylation at Thr389 is required for its activity and is blocked by rapamycin, 4E-BP1 is phosphorylated on multiple sites by mTOR, and it is the largely rapamycin-insensitive phosphorylation of Thr46 that prevents inhibitory binding to the 5’ mRNA cap-binding protein eIF4E [20,21]."
"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"
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)."
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."
reach
"[47] Following growth factor stimulation, S6K1 is phosphorylated by mTOR kinase at Thr229 on the activation loop and subsequently at Thr389 on the hydrophobic region by PDK1 [63]; once activated, S6K1 catalyzes the phosphorylation of the S6 ribosomal protein, thus playing a key role in the regulation of protein synthesis and cell growth."
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
"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."
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."