MAPK inactivation is required for the G2 to M-phase transition of the first mitotic cell cycle.
Down-regulation of MAP kinase (MAPK) is a universal consequence of fertilization in the animal kingdom, although its role is not known. Here we show that MAPK inactivation is essential for embryos, both vertebrate and invertebrate, to enter first mitosis. Suppressing down-regulation of MAPK at fertilization, for example by constitutively activating the upstream MAPK cascade, specifically suppresses cyclin B-cdc2 kinase activation and its consequence, entry into first mitosis. It thus appears that MAPK functions in meiotic maturation by preventing unfertilized eggs from proceeding into parthenogenetic development. The most general effect of artificially maintaining MAPK activity after fertilization is prevention of the G2 to M-phase transition in the first mitotic cell cycle, even though inappropriate reactivation of MAPK after fertilization may lead to metaphase arrest in vertebrates. Advancing the time of MAPK inactivation in fertilized eggs does not, however, speed up their entry into first mitosis. Thus, sustained activity of MAPK during part of the first mitotic cell cycle is not responsible for late entry of fertilized eggs into first mitosis.
Abrieu
A
A
Centre de Recherches de Biochimie Macromoléculaire, Montpellier, France.
Fisher
D
D
Simon
M N
MN
Dorée
M
M
Picard
A
A
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D054642:Dual Specificity Phosphatase 6; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000201:enzymology; D004789:Enzyme Activation; D005260:Female; D005306:Fertilization; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016195:G2 Phase / Q000502:physiology*; D020930:MAP Kinase Kinase Kinases; D008297:Male; D008540:Meiosis / Q000502:physiology; D008677:Metaphase / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D010312:Parthenogenesis / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins; D013215:Starfish / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology; D015053:Zygote / Q000166:cytology / Q000201:enzymology*
D019926:Cyclin B; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C071596:ste11 protein, S pombe; D011494:Protein Kinases; C102333:histone H1 kinase; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D019950:Mitogen-Activated Protein Kinase 1; D020930:MAP Kinase Kinase Kinases; D054642:Dual Specificity Phosphatase 6; D017027:Protein Tyrosine Phosphatases