K-252a inhibits nerve growth factor-induced trk proto-oncogene tyrosine phosphorylation and kinase activity

Margaret M. Berg, David W. Sternberg, Luis F. Parada, Moses V. Chao

Research output: Contribution to journalArticlepeer-review

311 Scopus citations

Abstract

The rat pheochromocytoma PC12 cell line differentiates into a sympathetic neuronal phenotype upon treatment with either nerve growth factor (NGF) or basic fibroblast growth factor. The alkaloid-like compound K-252a has been demonstrated to be a specific inhibitor of NGF-induced biological responses in PC12 cells (Koizumi, S., Contreras, M. L., Matsuda, Y., Hama, T., Lazarovici, P., and Guroff, G. (1988) J. Neurosci. Res. 8, 715-721). NGF interacts with the protein product of the proto-oncogene trk and rapidly stimulates the tyrosine phosphorylation of both p140(prototrk) and a number of cellular substrates. Here we show that these phosphorylation events are directly inhibited in PC12 cells by K252a in a dose-dependent manner, indicating that the site of action of this inhibitor is at the NGF receptor level. K-252a inhibits p140(prototrk) activity in vitro, demonstrating that K-252a has a direct effect on the p140(prototrk) tyrosine kinase. Though many of the biochemical responses to NGF in PC12 cells are mimicked by basic fibroblast growth factor and epidermal growth factor, K-252a has no effect on the action of these growth factors in PC12 cells, demonstrating that the initial biological events initiated by NGF are distinctive during neuronal differentiation.

Original languageEnglish (US)
Pages (from-to)13-16
Number of pages4
JournalJournal of Biological Chemistry
Volume267
Issue number1
StatePublished - 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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