title: Cell cycle arrest in the G2 phase induced by phorbol ester and diacylglycerol in vascular endothelial cells.
abstract: The role of protein kinase C (PKC) in vascular endothelial cell proliferation was investigated using human umbilical vein endothelial cells released from the G1/S border. Phorbol 12-myristate 13-acetate (PMA) caused G2 arrest because 1) when added to G2 cells, PMA inhibited subsequent cell division; 2) these growth-arrested cells did not show morphological features of mitotic cells; and 3) PMA did not interrupt mitosis in cells released from nocodazole-induced M phase arrest. 1-Oleoyl-2-acetyl-sn-glycerol (OAG) added repeatedly from G2 also inhibited mitosis. The activation of cdc2 kinase around the G2/M transition was suppressed by PMA and OAG. Although cdc2 was expressed in the presence of PMA, dephosphorylation of its tyrosine residue was inhibited by PMA. In parallel, the expression of cdc25B was suppressed by PMA. The total and the cdc2-associated amount of cyclin B were both reduced by PMA. These data suggested that the PKC pathway negatively regulates the G2/M transition and that the inhibition of cdc2 kinase by the reduction in the levels of cdc25B and cyclin B may contribute to this effect.
authors.affiliation: National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Kosaka
authors.forename: T
authors.initials: T
authors.lastname: Sasaguri
authors.forename: A
authors.initials: A
authors.lastname: Ishida
authors.forename: J
authors.initials: J
authors.lastname: Ogata
mesh_terms: D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D002453:Cell Cycle / Q000187:drug effects*; D004075:Diglycerides / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004789:Enzyme Activation; D016195:G2 Phase; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D004075:Diglycerides; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D016203:CDC2 Protein Kinase; D013755:Tetradecanoylphorbol Acetate