Early cell cycle diacylglycerol (DAG) content and protein kinase C (PKC) activity enhancement potentiates prostaglandin F2 alpha (PGF2 alpha) induced mitogenesis in Swiss 3T3 cells.
R59022, a diacylglycerol kinase inhibitor, enhances the prostaglandin F2 alpha (PGF2 alpha)-induced diacylglycerol (DAG) synthesis in Swiss 3T3 cells. It also potentiates the PGF2 alpha-mediated protein kinase C (PKC)-dependent 80 kDa protein (80K) phosphorylation and initiation of DNA replication. R59022 enhances the PGF2 alpha 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 PGF2 alpha mitogenic response. These results suggest that mitogenically triggered fluctuations in DAG content and PKC activity play a pivotal role in controlling the PGF2 alpha-induced DNA synthesis while insulin acts via a different mechanism.
Instituto de Investigaciones en Ingenieria Genetica y Biologia Molecular (INGEBI), Buenos Aires, Argentina.
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M
Goin
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O
Pignataro
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L
Jimenez de Asua
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D004261:DNA Replication; D019852:Diacylglycerol Kinase; D004075:Diglycerides / Q000378:metabolism*; D015237:Dinoprost / Q000502:physiology*; D007328:Insulin / Q000502:physiology; D051379:Mice; D010766:Phosphorylation; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000378:metabolism*; D011744:Pyrimidinones / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D004075:Diglycerides; D007328:Insulin; D011744:Pyrimidinones; D013844:Thiazoles; C047505:R 59022; D015237:Dinoprost; D010770:Phosphotransferases; D019852:Diacylglycerol Kinase; D011493:Protein Kinase C