Open AccessRegulation of protein kinase C activity in neuronal differentiation induced by the N-ras oncogene in PC-12 cells.
Author(s) -
J C Lacal,
Antonio Cuadrado,
Janet E. Jones,
Robert J. Trotta,
David Burstein,
Timothy M. Thomson,
A. Pellicer
Publication year - 1990
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.10.6.2983
Subject(s) - biology , protein kinase a , protein kinase c , microbiology and biotechnology , oncogene , c raf , cellular differentiation , kinase , cell culture , mitogen activated protein kinase kinase , map2k7 , cyclin dependent kinase 2 , cell , cell cycle , biochemistry , gene , genetics
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.This work was supported by grant PB88-0079 from Dirección de Investigación Científica y Técnica (J.C.L.); Public Health Service grants Ca16213 (A.P.), Ca16239 (A.P.), and NS21648 (D.E.B.) from the National Institutes of Health; Council for Tobacco Research grant 2466 (D.E.B.); and a grant from the Familial Dysautonomia Foundation (D.B.E.).Peer Reviewe