Inactivation of MAPK in mature oocytes triggers progression into mitosis via a Ca2+ -dependent pathway but without completion of S phase.
Unfertilized sea urchin eggs that are arrested at G1 phase after completion of meiosis contain a highly phosphorylated mitogen-activated protein (MAP) kinase (MAPK), the ERK-like protein (ERK-LP). Several data including our previous results show that ERK-LP is inactivated after fertilization, which agrees with results obtained in other species including Xenopus, starfish and mammals. The question is to elucidate the function of a high MAPK activity in sea urchin eggs. We report here that dephosphorylation of ERK-LP with very low concentrations of two MEK inhibitors, PD98059 or U0126, triggers entry into mitosis. Under these conditions, recurrent oscillations of the phosphorylation of ERK-LP and of a tyrosine residue in Cdc2 occur, and the intracellular Ca2+ level (Ca2+ i) progressively and slowly increases. Nuclear envelope breakdown and all mitotic events initiated after dephosphorylation of ERK-LP are inhibited when changes in Ca2+ i are prevented; however, they are independent of the intracellular pH. These results suggest that inactivation of a MEK-ERK pathway, normally induced after fertilization of sea urchin eggs, triggers entry into mitosis by altering Ca2+ i but cannot trigger full DNA replication. We discuss the hypothesis that neither inactivation nor activation of a MEK-ERK pathway is required for S phase completion in sea urchin egg.
Zhang
Wen Ling
WL
UMR 7622 CNRS, Université Paris 6, 9 Quai St Bernard, Case 24, 75252 Paris cedex 05, France.
Huitorel
Philippe
P
Geneviere
Anne-Marie
AM
Chiri
Sandrine
S
Ciapa
Brigitte
B
D000818:Animals; D002070:Butadienes / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004261:DNA Replication; D004791:Enzyme Inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016200:Maturation-Promoting Factor / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D016196:S Phase / Q000502:physiology*; D012617:Sea Urchins
D002070:Butadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009570:Nitriles; C113580:U 0126; D016200:Maturation-Promoting Factor; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium