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 ,
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 kinases family, and to the Ca(2+)/calmodulin-dependent protein kinases subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. This enzyme is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is required for long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, this protein can undergo autophosphorylation, resulting in CaM-independent activity. Two transcript variants encoding distinct isoforms have been identified for this gene.
General function
Enzyme
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Cellular localization
Cytoplasmic
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Ovarian function
Oogenesis
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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.
Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Nutt LK et al. Vertebrate female reproduction is limited by the oocyte stockpiles acquired during embryonic development. These are gradually depleted over the organism's lifetime through the process of apoptosis. The timer that triggers this cell death is yet to be identified. We used the Xenopus egg/oocyte system to examine the hypothesis that nutrient stores can regulate oocyte viability. We show that pentose-phosphate-pathway generation of NADPH is critical for oocyte survival and that the target of this regulation is caspase-2, previously shown to be required for oocyte death in mice. Pentose-phosphate-pathway-mediated inhibition of cell death was due to the inhibitory phosphorylation of caspase-2 by calcium/calmodulin-dependent protein kinase II (CaMKII). These data suggest that exhaustion of oocyte nutrients, resulting in an inability to generate NADPH, may contribute to ooctye apoptosis. These data also provide unexpected links between oocyte metabolism, CaMKII, and caspase-2.
Expression regulated by
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Ovarian localization
Oocyte
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Acetylcholine increases Ca(2+) influx by activation of CaMKII in mouse oocytes. Kang D et al. IP(3)-induced Ca(2+) release is the primary mechanism that is responsible for acetylcholine (ACh)-induced Ca(2+) oscillation. However, other mechanisms remain to explain intracellular Ca(2+) elevation. We here report that ACh induces Ca(2+) influx via T-type Ca(2+) channel by activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), and the ACh-induced Ca(2+) influx facilitates the generation of Ca(2+) oscillation in the mouse ovulated oocytes (oocytes(MII)). ACh increased Ca(2+) current by 50+/-21%, and produced Ca(2+) oscillation. However, the currents and Ca(2+) peaks were reduced in Ca(2+)-free extracellular medium. ACh failed to activate Ca(2+) current and to produce Ca(2+) oscillation in oocytes pretreated with KN-93, a CaMKII inhibitor. KN-92, an inactive analogue of KN93, and PKC modulators could not prevent the effect of ACh. These results show that ACh increases T-type Ca(2+) current by activation of CaMKII, independent of the PKC pathway, in the mouse oocytes.