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Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs

Naturevolume 366pages270273 (1993) | Download Citation

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Abstract

IN vertebrates, unfertilized eggs are arrested at second meiotic metaphase by a cytostatic factor (CSF)1, an essential component of which is the product of the c-mos proto-oncogene2. CSF prevents ubiquitin-dependent degradation of mitotic cyclins and thus inactivation of the M phase-promoting factor (MPF)3,4.Fertilization or parthenogenetic activation triggers a transient increase in the cytoplasmic free Ca2+ (reviewed in refs 5 and 6), inactivates both CSF and MPF, and releases eggs from meiotic metaphase arrest7–10. A calmodulin-dependent process is required for cyclin degradation to occur in cell-free extracts prepared from metaphase II-arrested eggs (CSF extracts) when the free Ca2+concentration is transiently raised in the physiological micromolar range10. Here we show that when a constitutively active mutant of calmodulin-dependent protein kinase II (CaM KII) is added to a CSF extract, cyclin degradation and Cdc2 kinase inactivation occur even in the absence of Ca2+, and the extract loses its ability to cause metaphase arrest when transferred into embryos. Furthermore, specific inhibitors of CaM KIIprevent cyclin degradation after calcium addition. Finally, the direct microinjection of constitutively active CaM KH into unfertilized eggs inactivates Cdc2 kinase and CSF, even in the absence of a Ca2+ transient. The target for Ca2+calmodulin is thus CaM KII.

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Affiliations

  1. Centre National de la Recherche Scientifique and Institut National de la Santé et de la Recherche Médicale, BP 5051, 34033, Montpellier Cedex, France

    • Thierry Lorca
    • , Didier Fesquet
    • , Jean-claude Cavadore
    • , Jean Méry
    •  & Marcel Dorée
  2. Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    • Francisco H. Cruzalegui
  3. Department of Pharmacology, Duke University Medical Center, Durham, North Carolina, 27710, USA

    • Anthony Means

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https://doi.org/10.1038/366270a0

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