Activation of translation initiation factor eIF2B by insulin requires phosphatidyl inositol 3-kinase

Gavin I. Welsh, Christa M. Stokes, Xuemin Wang, Hiroshi Sakaue, Wataru Ogawa, Masato Kasuga, Christopher G. Proud

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86 Citations (Scopus)


Eukaryotic initiation factor eIF2B mediates a key regulatory step in peptide-chain initiation and is acutely activated by insulin, although, it is not clear how. Inhibitors of phosphatidylinositide 3-kinase blocked activation of eIF2B, although rapamycin, which inhibits the p70 S6 kinase pathway, did not. Furthermore, a dominant negative mutant of PI 3-kinase also prevented activation of eIF2B, while a Sos-mutant, which blocks MAP kinase activation, did not. The data demonstrate that a pathway distinct from MAP and p70 S6 kinases regulates eIF2B. Glycogen synthase kinase-3 (GSK-3) phosphorylates and inactivates eIF2B. In all cases, eIF2B and GSK-3 were regulated reciprocally. Dominant negative PI 3-kinase abolished the insulin- induced inhibition of GSK-3. These data strongly support the hypothesis that insulin activates eIF2B through a signalling pathway involving PI 3-kinase and inhibition of GSK-3.

Original languageEnglish
Pages (from-to)418-422
Number of pages5
JournalFEBS Letters
Issue number2-3
Publication statusPublished - 30 Jun 1997
Externally publishedYes


  • Glycogen synthase kinase-3
  • Initiation factor
  • Insulin
  • Phosphatidylinositide 3- kinase
  • Protein synthesis
  • Wortmannin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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