Nerve growth factor induces rapid accumulation of the GTP-bound form of p21ras in rat pheochromocytoma PC12 cells

Oncogene. 1992 Feb;7(2):277-81.


The ras gene product (p21) is thought to transduce signals from various growth and differentiation factors. p21 is a GTP-binding protein, and its activity is regulated by the bound GDP/GTP ratio. We analysed p21-bound nucleotides in cell lysates of rat pheochromocytoma cell line PC12 cells stimulated with various factors. Nerve growth factors (NGF) rapidly increased the relative amount of active p21-GTP complex to as much as 20% of the total amount of p21 within 2 min. The amount of p21-GTP then declined to 8% after 10 min, and this level was sustained for at least 2 h. Epidermal growth factor (EGF) also stimulated a rapid accumulation of p21-GTP to the same extent as seen with NGF, but the amount of p21-GTP declined to 5% after 10 min and gradually returned to the basal level within 60 min. In contrast, basic fibroblast growth factor, interleukin 6 and dibutyryl cAMP, which induce neuronal differentiation of PC12 cells, did not stimulate the accumulation of p21-GTP at any time point examined. Phorbol 12-myristate 13-acetate also had no effect. Interestingly, the protein kinase inhibitor K-252a specifically suppressed the NGF-induced accumulation of p21-GTP, but did not suppress the EGF-induced response. These results strongly suggest that an active p21-GTP complex transduces the differentiation signal from NGF. It may also be suggested that the process of activating p21 is mediated by a K-252a-sensitive protein kinase(s).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbazoles / pharmacology
  • Epidermal Growth Factor / metabolism
  • GTP-Binding Proteins / metabolism*
  • Guanosine Triphosphate / metabolism*
  • In Vitro Techniques
  • Indole Alkaloids
  • Nerve Growth Factors / pharmacology*
  • PC12 Cells
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Rats
  • Signal Transduction / drug effects


  • Carbazoles
  • Indole Alkaloids
  • Nerve Growth Factors
  • Protein Kinase Inhibitors
  • Epidermal Growth Factor
  • Guanosine Triphosphate
  • staurosporine aglycone
  • GTP-Binding Proteins
  • Proto-Oncogene Proteins p21(ras)