Overexpression of the trk tyrosine kinase rapidly accelerates nerve growth factor-induced differentiation

Neuron. 1992 Nov;9(5):883-96. doi: 10.1016/0896-6273(92)90241-5.


To investigate the role of the gp140trk receptor tyrosine kinase in nerve growth factor (NGF)-induced differentiation, we have overexpressed gp140trk in the NGF-responsive PC12 cell line. Here we demonstrate that overexpression of gp140trk results in marked changes in NGF-induced differentiation. Whereas PC12 cells elaborated neurites after 2 days of continuous exposure to NGF, PC12 cells overexpressing gp140trk by 20-fold(trk-PC12) began this process within hours. Compared with wild-type PC12 cells, trk-PC12 exhibited an increase in both high and low affinity NGF-binding sites. Furthermore, trk-PC12 cells displayed an enhanced level of NGF-dependent gp140trk autophosphorylation, and this activity was sustained for many hours following ligand binding. The tyrosine phosphorylation or activity of several cellular proteins, such as PLC-gamma 1, PI-3 kinase, and Erk1 and the expression of the mRNA for the late response gene transin were also sustained as a consequence of gp140trk overexpression. The data indicate that overexpression of gp140trk in PC12 cells markedly accelerates NGF-induced differentiation pathways, possibly through the elevation of gp140trk tyrosine kinase activity.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / physiology*
  • Gene Expression*
  • Immunosorbent Techniques
  • Kinetics
  • Nerve Growth Factors / pharmacology*
  • Neurites / physiology
  • PC12 Cells / metabolism
  • Phosphorylation
  • Phosphotyrosine
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology*
  • RNA / metabolism
  • Rats
  • Receptor, trkA
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / physiology*
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • Nerve Growth Factors
  • Proto-Oncogene Proteins
  • Receptors, Nerve Growth Factor
  • Phosphotyrosine
  • Tyrosine
  • RNA
  • Receptor, trkA