Regulation of translation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway

Nicholas T. Redpath, Emily J. Foulstone, Christopher G. Proud

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It is well established that insulin and serum stimulate gene expression at the level of mRNA translation in animal cells, and previous studies have mainly focused on the initiation process. Here we show that, in Chinese hamster ovary cells expressing the human insulin receptor, insulin causes decreased phosphorylation of elongation factor eEF-2 and that this is associated with stimulation of the rate of peptide-chain elongation. eEF-2 is phosphorylated by a very specific Ca2+/calmodulin-dependent protein kinase (eEF-2 kinase) causing its complete inactivation. The decrease in eEF-2 phosphorylation induced by insulin reflects a fall in eEF-2 kinase activity. Rapamycin, a macrolide immunosuppressant which blocks the signalling pathway leading to the stimulation of the 70/85 M)a ribosomal protein S6 kinases, substantially blocks the activation of elongation, the fall in eEF-2 phosphorylation and the decrease in eEF-2 kinase activity, suggesting that p70 S6 kinase (p70(S6k)) and eEF-2 kinase may lie on a common signalling pathway. Wortmannin, an inhibitor of phosphatidylinositide-3-OH kinase, had similar effects. eEF-2 kinase was phosphorylated in vitro by purified p70(S6k) but this had no significant effect on the in vitro activity of eEF-2 kinase.

Original languageEnglish
Pages (from-to)2291-2297
Number of pages7
JournalEMBO Journal
Issue number9
Publication statusPublished - 1 May 1996
Externally publishedYes


  • Elongation factor-2
  • Elongation factor-2 kinase
  • Insulin
  • Phosphorylation
  • Rapamycin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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