R59022, a diacylglycerol kinase inhibitor, enhances the prostaglandin F2α (PGF2α)-induced diacylglycerol (DAG) synthesis in Swiss 3T3 cells. It also potentiates the PGF2α-mediated protein kinase C (PKC)-dependent 80 kDa protein (80K) phosphorylation and initiation of DNA replication. R 59022 enhances the PGF2α mitogenic response by increasing the rate of entry into the S phase. Insulin does not cause 80K phosphorylation, and does not enhance its induction but it potentiates the PGF2α mitogenic response. These results suggest that mitogenically triggered fluctuations in DAG content and PKC activity play a pivotal role in controlling the PGF2α-induced DNA synthesis while insulin acts via a different mechanism.
