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

Barbara L. Hempstead, Stuart J. Rabin, Leni Kaplan, Susan Reid, Luis F. Parada, David R. Kaplant

Research output: Contribution to journalArticlepeer-review

283 Scopus citations

Abstract

To investigate the role of the gp140trk receptor tyrosine kinase in nerve growth factor (NGF)-induced differentiation, we have overexpressed gpl40trk 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 overexpressiog 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-γ1, 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.

Original languageEnglish (US)
Pages (from-to)883-896
Number of pages14
JournalNeuron
Volume9
Issue number5
DOIs
StatePublished - Nov 1992

ASJC Scopus subject areas

  • Neuroscience(all)

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