Akt, a target of phosphatidylinositol 3-kinase, inhibits apoptosis in a differentiating neuronal cell line

Mol Cell Biol. 1998 Apr;18(4):2143-52. doi: 10.1128/mcb.18.4.2143.

Abstract

Phosphatidylinositol (PI) 3-kinase has been suggested to mediate cell survival. Consistent with this possibility, apoptosis of conditionally (simian virus 40 Tts) immortalized rat hippocampal H19-7 neuronal cells was increased in response to wortmannin, an inhibitor of PI 3-kinase. Downstream effectors of PI 3-kinase include Rac1, protein kinase C, and the serine-threonine kinase Akt (protein kinase B). Here, we show that activation of Akt is one mechanism by which PI 3-kinase can mediate survival of H19-7 cells during serum deprivation or differentiation. While ectopic expression of wild-type Akt (c-Akt) does not significantly enhance survival in H19-7 cells, expression of activated forms of Akt (v-Akt or myristoylated Akt) results in enhanced survival which can be comparable to that conferred by Bcl-2. Conversely, expression of a dominant-negative mutant of Akt accelerates cell death upon serum deprivation or differentiation. Finally, the results indicate that Akt can transduce a survival signal for differentiating neuronal cells through a mechanism that is independent of induction of Bcl-2 or Bcl-XL or inhibition of Jun kinase activity.

Publication types

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

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Apoptosis*
  • Cell Differentiation
  • Cell Line
  • Culture Media, Serum-Free
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Genes, Dominant
  • Mutation
  • Neurons / enzymology
  • Neurons / physiology*
  • Oncogene Protein v-akt
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Rats
  • Retroviridae Proteins, Oncogenic / metabolism
  • Wortmannin
  • bcl-X Protein

Substances

  • Androstadienes
  • Bcl2l1 protein, rat
  • Culture Media, Serum-Free
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Retroviridae Proteins, Oncogenic
  • bcl-X Protein
  • Protein-Tyrosine Kinases
  • Akt1 protein, rat
  • Oncogene Protein v-akt
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Wortmannin