Transactivation of the TPA-responsive element by the oncogenic C-erbB-2 protein is partly mediated by protein kinase C

Biochem Biophys Res Commun. 1991 Jul 31;178(2):724-32. doi: 10.1016/0006-291x(91)90168-7.

Abstract

The mutant c-erbB-2 gene encoding a protein with Glu instead of Val-659 in the transmembrane domain is able to transform NIH3T3 cells, while the wild type c-erbB-2 unless overexpressed does not. The mutant c-erbB-2 protein shows enhanced tyrosine kinase activity in vitro. Transient expression of this active c-erbB-2 stimulated the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element, serum response element, and cyclic AMP response element. Particularly, stimulation of the TPA response element by active c-erbB-2 was prominent. In contrast, transient expression of wild type c-erbB-2 stimulated none of these elements. Transactivation of the TPA response element was also observed in a cell line that stably expresses active c-erbB-2. The active c-erbB-2-induced transactivation of the TPA response element was partially prevented either by down-regulation of protein kinase C or by the protein kinase C inhibitor H7. These results indicate that protein kinase C is partly involved in oncogenic signalling of the active c-erbB-2 protein that leads to Jun/Fos-mediated transcriptional activation in nuclei.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Animals
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / genetics
  • Chloramphenicol O-Acetyltransferase / metabolism
  • DNA-Binding Proteins / genetics*
  • Gene Expression
  • Growth Hormone / genetics
  • Isoquinolines / pharmacology
  • Kinetics
  • Mice
  • Phosphorylation
  • Piperazines / pharmacology
  • Plasmids
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogenes*
  • RNA, Messenger / genetics
  • Receptor, ErbB-2
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transcription Factors / genetics*
  • Transcription, Genetic / drug effects
  • Transcriptional Activation*
  • Transfection

Substances

  • DNA-Binding Proteins
  • Isoquinolines
  • Piperazines
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Transcription Factors
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Growth Hormone
  • Chloramphenicol O-Acetyltransferase
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate