PMID- 8232587 OWN - NLM STAT- MEDLINE DCOM- 19931220 LR - 20131121 IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 366 IP - 6452 DP - 1993 Nov 18 TI - Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. PG - 270-3 AB - In vertebrates, unfertilized eggs are arrested at second meiotic metaphase by a cytostatic factor (CSF), an essential component of which is the product of the c-mos proto-oncogene. CSF prevents ubiquitin-dependent degradation of mitotic cyclins and thus inactivation or the M phase-promoting factor (MPF). 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 arrest. 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 range. 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 KII prevent cyclin degradation after calcium addition. Finally, the direct microinjection of constitutively active CaM KII into unfertilized eggs inactivates Cdc2 kinase and CSF, even in the absence of a Ca2+ transient. The target for Ca(2+)-calmodulin is thus CaM KII. FAU - Lorca, T AU - Lorca T AD - Centre National de la Recherche Scientifique, Montpellier, France. FAU - Cruzalegui, F H AU - Cruzalegui FH FAU - Fesquet, D AU - Fesquet D FAU - Cavadore, J C AU - Cavadore JC FAU - Mery, J AU - Mery J FAU - Means, A AU - Means A FAU - Doree, M AU - Doree M LA - eng PT - Journal Article PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Cyclins) RN - 0 (Peptide Fragments) RN - 0 (Recombinant Proteins) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-mos) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.18 (Myosin-Light-Chain Kinase) RN - EC 2.7.11.22 (CDC2 Protein Kinase) RN - EC 2.7.11.22 (Maturation-Promoting Factor) RN - SY7Q814VUP (Calcium) SB - IM CIN - Nature. 1993 Nov 18;366(6452):211-2. PMID: 8232578 MH - Amino Acid Sequence MH - Animals MH - CDC2 Protein Kinase/metabolism MH - Calcium/metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2 MH - Calcium-Calmodulin-Dependent Protein Kinases/genetics/*metabolism MH - Cells, Cultured MH - Cloning, Molecular MH - Cyclins/metabolism MH - Enzyme Activation MH - *Fertilization MH - Maturation-Promoting Factor/*antagonists & inhibitors MH - Molecular Sequence Data MH - Mutation MH - Myosin-Light-Chain Kinase/metabolism MH - Peptide Fragments/metabolism MH - Proto-Oncogene Proteins c-mos/*antagonists & inhibitors MH - Rats MH - Recombinant Proteins/metabolism MH - Xenopus EDAT- 1993/11/18 00:00 MHDA- 2000/03/11 09:00 CRDT- 1993/11/18 00:00 PHST- 1993/11/18 00:00 [pubmed] PHST- 2000/03/11 09:00 [medline] PHST- 1993/11/18 00:00 [entrez] AID - 10.1038/366270a0 [doi] PST - ppublish SO - Nature. 1993 Nov 18;366(6452):270-3. doi: 10.1038/366270a0.