Amino acid-dependent control of p70(s6k). Involvement of tRNA aminoacylation in the regulation - PubMed (original) (raw)
. 1999 Jan 8;274(2):1092-9.
doi: 10.1074/jbc.274.2.1092.
Affiliations
- PMID: 9873056
- DOI: 10.1074/jbc.274.2.1092
Free article
Amino acid-dependent control of p70(s6k). Involvement of tRNA aminoacylation in the regulation
Y Iiboshi et al. J Biol Chem. 1999.
Free article
Abstract
In human T-lymphoblastoid cells, downstream signaling events of mammalian target of rapamycin (mTOR), including the activity of p70(s6k) and phosphorylation of eukaryotic initiation factor 4E-binding protein 1, were dependent on amino acid concentration in the culture media, whereas other growth-related protein kinases were not. Amino acid-induced p70(s6k) activation was completely inhibited by rapamycin but only partially inhibited by wortmannin. Moreover, amino acid concentration similarly affected the p70(s6k) activity, which was dependent on a rapamycin-resistant mutant (S2035I) of mTOR. These data indicate that mTOR is required for amino acid-dependent activation of p70(s6k). The mechanism by which amino acids regulate p70(s6k) activity was further explored: 1) amino acid alcohols, which inhibit aminoacylation of tRNA by their competitive binding to tRNA synthetases, suppressed p70(s6k) activity; 2) suppression of p70(s6k) by amino acid depletion was blocked by cycloheximide or puromycin, which inhibit utilization of aminoacylated tRNA in cells; and 3) in cells having a temperature-sensitive mutant of histidyl tRNA synthetase, p70(s6k) was suppressed by a transition of cells to a nonpermissible temperature, which was partially restored by addition of high concentrations of histidine. These results indicate that suppression of tRNA aminoacylation is able to inhibit p70(s6k) activity. Deacylated tRNA may be a factor negatively regulating p70(s6k).
Similar articles
- Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism.
Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. Hara K, et al. J Biol Chem. 1998 Jun 5;273(23):14484-94. doi: 10.1074/jbc.273.23.14484. J Biol Chem. 1998. PMID: 9603962 - Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycinassociated protein.
Peterson RT, Desai BN, Hardwick JS, Schreiber SL. Peterson RT, et al. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4438-42. doi: 10.1073/pnas.96.8.4438. Proc Natl Acad Sci U S A. 1999. PMID: 10200280 Free PMC article. - Assessment of cell-signaling pathways in the regulation of mammalian target of rapamycin (mTOR) by amino acids in rat adipocytes.
Pham PT, Heydrick SJ, Fox HL, Kimball SR, Jefferson LS Jr, Lynch CJ. Pham PT, et al. J Cell Biochem. 2000 Sep 7;79(3):427-41. doi: 10.1002/1097-4644(20001201)79:3<427::aid-jcb80>3.0.co;2-0. J Cell Biochem. 2000. PMID: 10972980 - TOR action in mammalian cells and in Caenorhabditis elegans.
Long X, Müller F, Avruch J. Long X, et al. Curr Top Microbiol Immunol. 2004;279:115-38. doi: 10.1007/978-3-642-18930-2_8. Curr Top Microbiol Immunol. 2004. PMID: 14560955 Review.
Cited by
- Prolonged deprivation of arginine or leucine induces PI3K/Akt-dependent reactivation of mTORC1.
Buel GR, Dang HQ, Asara JM, Blenis J, Mutvei AP. Buel GR, et al. J Biol Chem. 2022 Jun;298(6):102030. doi: 10.1016/j.jbc.2022.102030. Epub 2022 May 13. J Biol Chem. 2022. PMID: 35577075 Free PMC article. - Repurposing Tranexamic Acid as an Anticancer Agent.
Law ME, Davis BJ, Ghilardi AF, Yaaghubi E, Dulloo ZM, Wang M, Guryanova OA, Heldermon CD, Jahn SC, Castellano RK, Law BK. Law ME, et al. Front Pharmacol. 2022 Jan 13;12:792600. doi: 10.3389/fphar.2021.792600. eCollection 2021. Front Pharmacol. 2022. PMID: 35095503 Free PMC article. - Methionine Supplementation Affects Metabolism and Reduces Tumor Aggressiveness in Liver Cancer Cells.
Tripodi F, Badone B, Vescovi M, Milanesi R, Nonnis S, Maffioli E, Bonanomi M, Gaglio D, Tedeschi G, Coccetti P. Tripodi F, et al. Cells. 2020 Nov 16;9(11):2491. doi: 10.3390/cells9112491. Cells. 2020. PMID: 33207837 Free PMC article. - Molecular basis of the multifaceted functions of human leucyl-tRNA synthetase in protein synthesis and beyond.
Liu RJ, Long T, Li H, Zhao J, Li J, Wang M, Palencia A, Lin J, Cusack S, Wang ED. Liu RJ, et al. Nucleic Acids Res. 2020 May 21;48(9):4946-4959. doi: 10.1093/nar/gkaa189. Nucleic Acids Res. 2020. PMID: 32232361 Free PMC article. - A randomized 3-way crossover study indicates that high-protein feeding induces de novo lipogenesis in healthy humans.
Charidemou E, Ashmore T, Li X, McNally BD, West JA, Liggi S, Harvey M, Orford E, Griffin JL. Charidemou E, et al. JCI Insight. 2019 May 30;4(12):e124819. doi: 10.1172/jci.insight.124819. eCollection 2019 Jun 20. JCI Insight. 2019. PMID: 31145699 Free PMC article. Clinical Trial.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous