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 Synonyms: CaM KINASE II GAMMA SUBUNIT|  Locus: 10q22 in Homo sapiens

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General Comment Calcium/calmodulin-dependent protein kinase II (CaM kinase II) is a ubiquitous serine/threonine protein kinase that has been implicated in diverse effects of hormones and neurotransmitters that utilize Ca2+ as a second messenger. The enzyme is an oligomeric protein composed of distinct but related subunits, alpha (OMIM 114078), beta, gamma, and delta, each encoded by a separate gene. Each subunit has alternatively spliced variants.

NCBI Summary: The product of this gene belongs to the Serine/Threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a gamma chain. Six alternatively spliced variants that encode six different isoforms have been characterized to date. Additional alternative splice variants that encode different isoforms have been described, but their full-length nature has not been determined.
General function Enzyme
Comment The Regulation of Calcium/Calmodulin-dependent Protein Kinase II during Oocyte Activation in the Rat. Ito J et al. Increases in intracellular Ca(2+) 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 Ca(2+) 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 p34(cdc2) kinase and somewhat involved in degradation of Mos. Furthermore, CaMKII phosphorylation is negatively regulated by a protein phosphatase.
Cellular localization Cytoplasmic
Ovarian function Oogenesis, Oocyte maturation
Comment Calmodulin-dependent protein kinase gamma 3 (CamKII{gamma}3) mediates the cell cycle resumption of metaphase II eggs in mouse. Chang HY et al. Mature mammalian eggs are ovulated arrested at meiotic metaphase II. Sperm break this arrest by an oscillatory Ca(2+) signal that is necessary and sufficient for the two immediate events of egg activation: cell cycle resumption and cortical granule release. Previous work has suggested that cell cycle resumption, but not cortical granule release, is mediated by calmodulin-dependent protein kinase II (CamKII). Here we find that mouse eggs contain detectable levels of only one CamKII isoform, gamma 3. Antisense morpholino knockdown of CamKIIgamma3 during oocyte maturation produces metaphase II eggs that are insensitive to parthenogenetic activation by Ca(2+) stimulation and insemination. The effect is specific to this morpholino, as a 5-base-mismatch morpholino is without effect, and is rescued by CamKIIgamma3 or constitutively active CamKII cRNAs. Although CamKII-morpholino-treated eggs fail to exit metaphase II arrest, cortical granule exocytosis is not blocked. Therefore, CamKIIgamma3 plays a necessary and sufficient role in transducing the oscillatory Ca(2+) signal into cell cycle resumption, but not into cortical granule release. Su YQ, and Eppig JJ 2002 reported evidence that multifunctional calcium/calmodulin-dependent protein kinase II (CaM KII) participates in the meiotic maturation of mouse oocytes. Calcium-dependent signaling pathways are thought to be involved in the regulation of mammalian oocyte meiotic maturation. However, the molecular linkages between the calcium signal and the processes driving meiotic maturation are not clearly defined. The present study was conducted to test the hypothesis that the multi-functional calcium/calmodulin-dependent protein kinase II (CaM KII) functions as one of these key linkers. Mouse oocytes were treated with a pharmacological CaM KII inhibitor, KN-93, or a pepticle CaM KII inhibitor, myristoylated AIP, and assessed for the progression of meiosis, Two systems for in vitro oocyte maturation were used: (1) spontaneous gonadotropin-independent maturation and (2) follicle-stimulating hormone (FSH)-induced reversal of hypoxanthine-mediated meiotic arrest. FSH-induced, but not spontaneous germinal vesicle breakdown (GVB) was dose-dependently inhibited by both myristoylated AT and KN-93, but not its inactive analog, KN-92. However, emission of the first polar body (PB1) was inhibited by myristoylated AIP and KN-93 in both oocyte maturation systems. Oocytes that failed to produce PB1 exhibited normal-appearing metaphase I chromosome congression and spindles indicating that CaM KII inhibitors blocked the metaphase I to anaphase I transition. Similar results were obtained when the oocytes were treated with a calmodulin antagonist, W-7, and matured spontaneously. These results suggest that CaM KII, and hence the calcium signaling pathway, is potentially involved in regulating the meiotic maturation of mouse oocytes. This kinase both participates in gonadotropin-induced resumption of meiosis, as well as promoting the metaphase I to anaphase I transition. Further evidence is therefore, provided of the critical role of calcium-dependent pathways in mammalian oocyte maturation.
Expression regulated by
Ovarian localization Oocyte
Follicle stages Secondary, Antral, Preovulatory
Comment Differential expression of signal transduction factors in ovarian follicle development; a role for betaglycan FIBP in granulosa cells in cattle. Forde N et al. Ovarian follicles develop in groups yet individual follicles follow different growth trajectories. This growth and development is regulated by endocrine and locally produced growth factors that use a myriad of receptors and signal transduction pathways to exert their effects on theca and granulosa cells. We hypothesise that differential growth may be due to differences in hormonal responsiveness that is partially mediated by differences in expression of genes involved in signal transduction. We used the bovine dominant follicle model, microarrays, quantative real time PCR and RNA interference to examine this. We identified 83 genes coding for signal transduction molecules and validated a subset of them associated with different stages of the follicle wave. We suggest important roles for CAMkinase1 and EphA4 in theca cells and BCAR1 in granulosa cells for the development of dominant follicles and for betaglycan and FIBP in granulosa cells of regressing subordinate follicles. Inhibition of genes for betaglycan and FIBP in granulosa cells in vitro suggests that they inhibit estradiol production in regressing subordinate follicles. Key words: Follicle, FIBP, Betaglycan, Signalling, siRNA.
Mutations 0 mutations
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created: March 26, 2002, 8:30 a.m. by: hsueh   email:
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last update: Nov. 18, 2009, 11:18 a.m. by: hsueh    email:

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