PMID- 16040245 OWN - NLM STAT- MEDLINE DCOM- 20060216 LR - 20211203 IS - 0960-9822 (Print) IS - 0960-9822 (Linking) VI - 15 IP - 16 DP - 2005 Aug 23 TI - Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor. PG - 1458-68 AB - BACKGROUND: Vertebrate oocytes are arrested at second meiotic metaphase by cytostatic factor (CSF) while awaiting fertilization. Accumulating evidence has suggested that inhibition of the anaphase-promoting complex/cyclosome (APC/C) is responsible for this arrest. Xenopus polo-like kinase 1 (Plx1) is required for activation of the APC/C at the metaphase-anaphase transition, and calcium elevation, upon fertilization/activation of eggs, acting through calmodulin-dependent kinase II (CaMKII) is sufficient to activate the APC/C and terminate CSF arrest. However, connections between the Plx1 pathway and the CaMKII pathway have not been identified. RESULTS: Overexpression of Plx1 causes CSF release in the absence of calcium, and depletion of Plx1 from egg extracts blocks induction of CSF release by calcium and CaMKII. Prior phosphorylation of the APC/C inhibitor XErp1/Emi2 by CaMK II renders it a good substrate for Plx1, and phosphorylation by both kinases together promotes its degradation in egg extracts. The pathway is enhanced by the ability of Plx1 to cause calcium-independent activation of CaMKII. The results identify the targets of CaMKII and Plx1 that promote egg activation and define the first known pathway of CSF release in which an APC/C inhibitor is targeted for degradation only when both CaMKII and Plx1 are active after calcium elevation at fertilization. CONCLUSIONS: Plx1 with an intact polo-box domain is necessary for release of CSF arrest and sufficient when overexpressed. It acts at the same level as CaMKII in the pathway of calcium-induced CSF release by cooperating with CaMKII to regulate APC/C regulator(s), such as XErp1/Emi2, rather than by directly activating the APC/C itself. FAU - Liu, Junjun AU - Liu J AD - Howard Hughes Medical Institute and Department of Pharmacology, University of Colorado School of Medicine, Denver, Colorado 80262, USA. FAU - Maller, James L AU - Maller JL LA - eng GR - CA46930/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Curr Biol JT - Current biology : CB JID - 9107782 RN - 0 (Cell Cycle Proteins) RN - 0 (DNA Primers) RN - 0 (F-Box Proteins) RN - 0 (FBXO43 protein, Xenopus) RN - 0 (Xenopus Proteins) RN - EC 2.3.2.23 (Ubiquitin-Protein Ligase Complexes) RN - EC 2.3.2.27 (Anaphase-Promoting Complex-Cyclosome) RN - EC 2.7.11.1 (Plk1 protein, Xenopus) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) 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 - SY7Q814VUP (Calcium) SB - IM MH - Anaphase-Promoting Complex-Cyclosome MH - Animals MH - Calcium/*metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2 MH - Calcium-Calmodulin-Dependent Protein Kinases/metabolism MH - Cell Cycle Proteins/genetics/*metabolism MH - Cell Nucleus/ultrastructure MH - Cloning, Molecular MH - DNA Primers MH - F-Box Proteins/*metabolism MH - Fertilization/*physiology MH - Immunoblotting MH - Male MH - Metaphase/*physiology MH - Oocytes/metabolism/*physiology MH - Phosphorylation MH - Protein Serine-Threonine Kinases/genetics/*metabolism MH - Proto-Oncogene Proteins c-mos/metabolism MH - Signal Transduction/*physiology MH - Spermatozoa/ultrastructure MH - Ubiquitin-Protein Ligase Complexes/metabolism MH - Xenopus MH - Xenopus Proteins/genetics/*metabolism EDAT- 2005/07/26 09:00 MHDA- 2006/02/17 09:00 CRDT- 2005/07/26 09:00 PHST- 2005/05/18 00:00 [received] PHST- 2005/06/30 00:00 [revised] PHST- 2005/07/08 00:00 [accepted] PHST- 2005/07/26 09:00 [pubmed] PHST- 2006/02/17 09:00 [medline] PHST- 2005/07/26 09:00 [entrez] AID - S0960-9822(05)00774-8 [pii] AID - 10.1016/j.cub.2005.07.030 [doi] PST - ppublish SO - Curr Biol. 2005 Aug 23;15(16):1458-68. doi: 10.1016/j.cub.2005.07.030.