Stimulatory effect of okadaic acid, an inhibitor of protein phosphatases, on nuclear envelope breakdown and protein phosphorylation in mouse oocytes and one-cell embryos.
Treatment of one-cell mouse embryos with okadaic acid (OA), which is an inhibitor of protein phosphatases 1 and 2A, induces a concentration-dependent precocious nuclear envelope breakdown (NEBD) of the pronuclei; at 10 microM okadaic acid, NEBD starts to occur after 1 hr and the embryos become committed to NEBD after about 45 min. Correlated with NEBD is the conversion of a protein of Mr 32,000 (p32) to more highly phosphorylated forms. One-cell embryos cultured continuously in OA-containing medium do not cleave, whereas one-cell embryos incubated for 15-60 min prior to transfer to OA-free medium reveal a time-dependent inhibition in their ability to cleave. OA treatment of oocytes that are arrested from resuming spontaneous maturation by either a phosphodiesterase inhibitor or biologically active phorbol diester results in germinal vesicle breakdown and the maturation-associated changes in the pattern of protein phosphorylation, which include the apparent phosphorylation of p32. Results of these experiments implicate protein phosphatases in the G2 to M transition of the cell cycle in both meiotic and mitotic cells.
Schwartz
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DA
Department of Biology, University of Pennsylvania, Philadelphia 19104-6018.
Schultz
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RM
D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000502:physiology*; D004527:Egg Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009685:Nuclear Envelope / Q000187:drug effects / Q000502:physiology*; D019319:Okadaic Acid; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010710:Phosphates; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation
D004527:Egg Proteins; D004988:Ethers, Cyclic; D010710:Phosphates; D010750:Phosphoproteins; D019319:Okadaic Acid; D008715:Methionine; D010749:Phosphoprotein Phosphatases