Akt Phosphorylation Is Essential for Nuclear Translocation and Retention in NGF-stimulated PC12 Cells

Biochem Biophys Res Commun. 2006 Oct 20;349(2):789-98. doi: 10.1016/j.bbrc.2006.08.120. Epub 2006 Aug 28.


Nerve growth factor (NGF) elicits Akt translocation into the nucleus, where it phosphorylates nuclear targets. Here, we describe that Akt phosphorylation can promote the nuclear translocation of Akt and is necessary for its nuclear retention. Overexpression of Akt-K179A, T308A, S473A-mutant failed to show either nuclear translocation or nuclear Akt phosphorylation, whereas expression of wild-type counterpart elicited profound Akt phosphorylation and induced nuclear translocation under NGF stimulation. Employing the PI3K inhibitor and a variety of mutants PI3K, we showed that nuclear translocation of Akt was mediated by activation of PI3K, and Akt phosphorylation status in the nucleus required PI3K activity. Thus the activity of PI3K might contribute to the nuclear translocation of Akt, and that Akt phosphorylation is essential for its nuclear retention under NGF stimulation conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus*
  • Animals
  • Enzyme Activation
  • Green Fluorescent Proteins / metabolism
  • Male
  • Mutation
  • Nerve Growth Factor / metabolism*
  • PC12 Cells
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Prostatic Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-akt / chemistry*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Subcellular Fractions / metabolism


  • Green Fluorescent Proteins
  • Nerve Growth Factor
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt