The diacylglycerol kinase inhibitor R 59022 potentiates bombesin stimulation of protein kinase C activity and DNA synthesis in Swiss 3T3 cells.
Addition of the inhibitor of diacylglycerol kinase R 59022 to quiescent Swiss 3T3 cells potentiated protein kinase C activation by the neuropeptide bombesin, a potent mitogen for these cells. This was detected as a marked shift in the dose-response relationship for bombesin-stimulated phosphorylation of a Mr 80,000 protein, which is a major, specific substrate of protein kinase C. R 59022 also promoted the inhibition of [125I]epidermal growth factor binding induced by bombesin, an effect mediated by protein kinase C. A salient feature of our results is that R 59022, at concentrations that enhanced the activation of protein kinase C in intact cells (4-6 microM), potentiated long-term mitogenesis elicited by bombesin. Thus, R 59022 may be a valuable tool for elucidating the contribution of the protein kinase C pathway in mitogenesis.
Morris
C
C
Imperial Cancer Research Fund, London.
Rice
P
P
Rozengurt
E
E
D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects*; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000032:analysis; D011493:Protein Kinase C / Q000378:metabolism*; D011744:Pyrimidinones / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D010750:Phosphoproteins; D011744:Pyrimidinones; D013844:Thiazoles; D004815:Epidermal Growth Factor; C047505:R 59022; D011493:Protein Kinase C; D001839:Bombesin