p21(ras) stimulates pathways in addition to ERK, p38, and Akt to induce elongation of neurites in PC12 cells

J Neurosci Res. 2001 Jan 1;63(1):45-53. doi: 10.1002/1097-4547(20010101)63:1<45::AID-JNR6>3.0.CO;2-Y.

Abstract

Initiation and elongation of neurites in PC12 cells has been shown to be stimulated by nerve growth factor (NGF). Initiation of NGF-stimulated neurites in a PC12 subclone (PC12-N09) is rapid, giving rise to short neurites that do not elongate after 1 day. To determine whether increasing activation of p21(ras) could restore neurite elongation in these cells and whether it would affect the phosphorylation of signaling proteins, the subclone PC12-N09 was transfected with constitutively active p21(ras61L) (PC12-N09ras61L) and neurite outgrowth with or without NGF was determined. Overexpression of wild-type p21(ras) (PC12-N09rasWT) did not lead to spontaneous neurite initiation but restored the ability of NGF to stimulate continuous neurite elongation. However, NGF-stimulated phosphorylation of ERK, p38, and Akt in PC12-N09rasWT cells is similar in duration to that in PC12-N09 cells, indicating that the p21(ras) signaling through ERK, p38, and Akt was not involved in the restoration of normal neurite elongation in PC12-N09 cells. These results show that p21(ras)-activated pathways other than ERK, p38, and Akt are necessary for appropriate NGF-stimulated neurite elongation in PC12 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Size / drug effects
  • Cell Size / physiology*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Nerve Growth Factor / metabolism*
  • Nerve Growth Factor / pharmacology
  • Neurites / drug effects
  • Neurites / metabolism*
  • Neurites / ultrastructure
  • PC12 Cells / cytology
  • PC12 Cells / drug effects
  • PC12 Cells / metabolism*
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-fos / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Rats
  • Transfection
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fos
  • Nerve Growth Factor
  • Akt1 protein, rat
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Proto-Oncogene Proteins p21(ras)