Regulation of the activity of M-phase promoting factor through protein kinase A-mediated pathway in LP1-1 cells.
Treatment of cAMP analogs, dibutyryl cAMP and 8-bromo-cAMP, was found to inhibit the proliferation of mouse fibroblast LP1-1 cells and the p34cdc2 kinase activity of M-phase promoting factor (MPF). However, it showed relatively little effect on expression of the cyclin B1 and cdc2 genes. On the other hand, when the nuclear extracts obtained from the cells at early G2 phase were treated with cAMP analogs, the kinase activity was significantly decreased as compared to the untreated control. Furthermore, the inhibitory effect of cAMP analogs could be reversed upon treating with okadaic acid even in the presence of the cAMP analogs, implying that cdc25 remains in an active form. In addition, the treatment of okadaic acid stimulated the cell progression. These results suggest that down-regulation of MPF activity through protein kinase A-mediated pathway is under post-translational control and cdc25 activation pathway involving okadaic acid-sensitive phosphatase play a role in the regulation of MPF activity.
Oh
W J
WJ
Department of Biology, College of Natural Sciences, Chung-Ang University, Seoul, Korea.
Joe
C O
CO
Choi
K H
KH
D000818:Animals; D016203:CDC2 Protein Kinase / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D016195:G2 Phase / Q000502:physiology; D016200:Maturation-Promoting Factor / Q000187:drug effects / Q000378:metabolism*; D000090204:Mesothelin; D051379:Mice; D008938:Mitosis / Q000502:physiology; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D016196:S Phase / Q000502:physiology; D015398:Signal Transduction; D013936:Thymidine / Q000378:metabolism
D016213:Cyclins; C000715528:Msln protein, mouse; D019319:Okadaic Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor; D000090204:Mesothelin; D013936:Thymidine