title: The regulation of calcium/calmodulin-dependent protein kinase II during oocyte activation in the rat.
abstract: Increases in intracellular Ca2+ are required for oocyte activation and subsequent development. Calmodulin-dependent protein kinase II (CaMKII) plays a crucial role in oocyte activation. However, how CaMKII is regulated during this process is not well characterized. We show here for the first time in rat oocytes that CaMKII is phosphorylated during oocyte activation. CaMKII phosphorylation was suppressed by KN93, a CaMKII inhibitor, but not KN92, which is the inactive analogue of KN93. Electrical stimulation of rat oocytes resulted in degradation of both cyclin B and Mos, presumably due a rise in Ca2+ induced by the electrical pulse. KN93 blocked the degradation of both proteins induced by the electrical pulse. Addition of a protein phosphatase inhibitor, okadaic acid (OA), further increased the amount of CaMKII and also increased the amount of phosphorylated enzyme. Importantly, in oocytes undergoing spontaneous activation, accumulation and phosphorylation of CaMKII also occurs in a time-dependent manner. Consistent with this, addition of KN93 inhibited spontaneous activation. Collectively, our results show that CaMKII is phosphorylated during oocyte activation and that this phosphorylation is involved in inactivation of p34cdc2 kinase and somewhat involved in degradation of Mos. Furthermore, CaMKII phosphorylation is negatively regulated by a protein phosphatase.
authors.affiliation: Section of Molecular Genetics, Center for Brain Experiment, National Institute for Physiological Sciences, Aichi, Japan. jito@vasci.umass.edu
authors.forename: Junya
authors.initials: J
authors.lastname: Ito
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kaneko
authors.forename: Masumi
authors.initials: M
authors.lastname: Hirabayashi
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism* / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D017231:Proto-Oncogene Proteins c-mos / Q000378:metabolism; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D000095043:Cyclin-Dependent Kinase-Activating Kinase; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018844:Cyclin-Dependent Kinases; D010749:Phosphoprotein Phosphatases; D047428:Protein Kinase Inhibitors; D017231:Proto-Oncogene Proteins c-mos; D013449:Sulfonamides; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C072105:KN 93; D000096926:Benzenesulfonamides