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

FEBS Lett. 1997 Jun 30;410(2-3):418-22. doi: 10.1016/s0014-5793(97)00579-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • CHO Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cricetinae
  • Enzyme Inhibitors / pharmacology
  • Eukaryotic Initiation Factor-2 / metabolism*
  • Eukaryotic Initiation Factor-2B
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Guanine Nucleotide Exchange Factors
  • Humans
  • Insulin / physiology*
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Proteins / metabolism*
  • Signal Transduction
  • Wortmannin


  • Androstadienes
  • Enzyme Inhibitors
  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factor-2B
  • Guanine Nucleotide Exchange Factors
  • Insulin
  • Proteins
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Glycogen Synthase Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3
  • Wortmannin