Regulation of protein kinase C activity in neuronal differentiation induced by the N-ras oncogene in PC-12 cells.
Expression of the N-ras oncogene under the control of the glucocorticoid-responsive promoter in the pheochromocytoma cell line UR61, a subline of PC-12 cells, has been used to investigate the differentiation process to neuronal cells triggered by ras oncogenes (I. Guerrero, A. Pellicer, and D. E. Burstein, Biochem. Biophys. Res. Commun. 150:1185-1192, 1988). Using ras-inducible cell lines, we observed that expression of the oncogenic N-ras p21 protein interferes with the ability of phorbol esters to induce downregulation of protein kinase C. This effect was associated with the appearance of immunologically detectable protein kinase C as well as the activity of the enzyme as analyzed either by binding of [3H]phorbol-12,13-dibutyrate in intact cells or by in vitro kinase activity. These results indicate a relationship between ras p21 and protein kinase C in neuronal differentiation in this model system. Comparison to the murine fibroblast system suggests that this relationship may be functional.
Instituto de Investigaciones Biomedicas, Madrid, Spain.
J C
JC
Lacal
A
A
Cuadrado
J E
JE
Jones
R
R
Trotta
D E
DE
Burstein
T
T
Thomson
A
A
Pellicer
D000310:Adrenal Gland Neoplasms; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006706:Homeostasis; D007700:Kinetics; D009474:Neurons / Q000166:cytology*; D015689:Oncogene Protein p21(ras) / Q000235:genetics*; D010673:Pheochromocytoma; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology*
D012333:RNA, Messenger; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D015689:Oncogene Protein p21(ras)