IGF-I promotes Schwann cell motility and survival via activation of Akt

Mol Cell Endocrinol. 2000 Dec 22;170(1-2):211-5. doi: 10.1016/s0303-7207(00)00324-5.

Abstract

We previously reported insulin-like growth factor-I (IGF-I) promotes Schwann cell (SC) motility and rescues SC from apoptosis induced by serum deprivation. This effect is mediated by phosphatidylinositol-3 (PI-3) kinase. In the current study, we examined the role of Akt, a downstream kinase of PI-3K, in SC motility and IGF-I mediated protection from apoptosis. IGF-I induces Akt phosphorylation at Ser473, an event which may be blocked by pretreatment with a PI-3K inhibitor, LY294002. In dominant negative K179M Akt (K179M) transfected SC, however, Akt is not activated in response to IGF-I. In addition, IGF-I is unable to promote SC motility and survival in K179M SC. These results suggest a critical role for Akt in IGF-I mediated motility and survival in SC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Mutation, Missense
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / pharmacology*
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Sprague-Dawley
  • Schwann Cells / cytology*
  • Schwann Cells / drug effects
  • Transfection

Substances

  • Proto-Oncogene Proteins
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Akt1 protein, rat
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt