Transactivation of the TPA-responsive element by the oncogenic C-erbB-2 protein is partly mediated by protein kinase C.
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.
Fujimoto
A
A
Department of Oncology, University of Tokyo, Japan.
Kai
S
S
Akiyama
T
T
Toyoshima
K
K
Kaibuchi
K
K
Takai
Y
Y
Yamamoto
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D010957:Plasmids; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015500:Chloramphenicol O-Acetyltransferase; D004268:DNA-Binding Proteins; D013006:Growth Hormone; D007546:Isoquinolines; D010879:Piperazines; D011493:Protein Kinase C; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate; D014157:Transcription Factors