Amino acid-dependent control of p70(s6k). Involvement of tRNA aminoacylation in the regulation

Yasuhiko Iiboshi, Philip J. Papst, Hideki Kawasome, Hajime Hosoi, Robert T. Abraham, Peter J. Houghton, Naohiro Terada

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)1092-1099
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number2
DOIs
StatePublished - Jan 8 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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