Involvement of functional protein kinase C in the mitogenic response to the H-ras oncogene product.
Microinjection of purified protein kinase C (PKC) into Swiss 3T3 fibroblasts pretreated with the phorbol ester phorbol-12,13-dibutyrate restores the mitogenic response of the cells to phorbol-12,13-dibutyrate (G. Pasti, J.C. Lacal, B.S. Warren, S.A. Aaronson, and P.M. Blumberg, Nature [London] 324:375-377, 1986). Our present studies demonstrate that the mitogenic activity of the H-ras oncogene in H-ras p21-microinjected quiescent cells is markedly reduced under conditions in which PKC is downregulated by chronic phorbol ester treatment. The ability to reconstitute the mitogenic response upon microinjection of both H-ras p21 and PKC implies involvement of functional PKC in the mitogenic activity of the H-ras oncogene product.
Lacal
J C
JC
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Fleming
T P
TP
Warren
B S
BS
Blumberg
P M
PM
Aaronson
S A
SA
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004261:DNA Replication; D011905:Genes, ras; D051379:Mice; D008815:Mice, Inbred Strains; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras)
D002273:Carcinogens; D010703:Phorbol Esters; D011518:Proto-Oncogene Proteins; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D016283:Proto-Oncogene Proteins p21(ras)