Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early metazoan development is programmed by maternal mRNAs inherited by the egg at the time of fertilization. These mRNAs are not translated en masse at any one time or at any one place, but instead their expression is regulated both temporally and spatially. Recent evidence has shown that one maternal mRNA, cyclin B1, is concentrated on mitotic spindles in the early Xenopus embryo, where its translation is controlled by CPEB (cytoplasmic polyadenylation element binding protein), a sequence-specific RNA binding protein. Disruption of the spindle-associated translation of this mRNA results in a morphologically abnormal mitotic apparatus and inhibited cell division. Mammalian neurons, particularly in the synapto-dendritic compartment, also contain localized mRNAs such as that encoding alpha-CaMKII. Here, synaptic activation drives local translation, an event that is involved in synaptic plasticity and possibly long-term memory storage. Synaptic translation of alpha-CaMKII mRNA also appears to be controlled by CPEB, which is enriched in the postsynaptic density. Therefore, CPEB-controlled local translation may influence such seemingly disparate processes as the cell cycle and synaptic plasticity.
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PMID:Think globally, translate locally: what mitotic spindles and neuronal synapses have in common. 1141 89

A dramatic increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) occurs in eggs at fertilization common to all animal species examined to date, and this serves as a pivotal signal for egg activation characterized by resumption of meiotic cell division and formation of the pronuclei. In mammalian eggs, repetitive [Ca(2+)](i) rises (Ca(2+) oscillations) each of which accompanies a propagating wave across the egg occur due to release of Ca(2+) from the endoplasmic reticulum mainly through type 1 inositol 1,4,5-trisphosphate (IP(3)) receptor. Ca(2+) oscillations are induced by a cytosolic sperm factor driven into the egg cytoplasm upon sperm-egg fusion. A current strong candidate of the sperm factor is a novel sperm-specific isozyme of phospholipase C (IP(3)-producing enzyme), PLCzeta. Recent extensive research has reveled characteristics of PLCzeta such as the Ca(2+) oscillation-inducing activity after injection of PLCzeta-encoding RNA or recombinant PLCzeta into mouse eggs, extremely high Ca(2+)-sensitivity of the enzymatic activity in vitro, and nuclear translocation ability possibly related to cell-cycle-dependent regulation of Ca(2+) oscillations. [Ca(2+)](i) rises cause successive activation of calmodulin-dependent kinase II and E3 ubiquitin ligase, lead to proteolysis of ubiquitinated cyclin B1 and inactivation of metaphase-promoting factor (Cdk1/cyclin B1 complex), and result in the release of eggs from meiotic arrest.
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PMID:Calcium signals for egg activation in mammals. 1679 64

M-phase Promoting Factor (MPF; the cyclin B-cdk 1 complex) is activated at M-phase onset by removal of inhibitory phosphorylation of cdk1 at thr-14 and tyr-15. At M-phase exit, MPF is destroyed by ubiquitin-dependent cyclin proteolysis. Thus, control of MPF activity via inhibitory phosphorylation is believed to be particularly crucial in regulating transition into, rather than out of, M-phase. Using the in vitro cell cycle system derived form Xenopus eggs, here we show, however, that inhibitory phosphorylation of cdk1 contributes to control MPF activity during M-phase exit. By sampling extracts at very short intervals during both meiotic and mitotic exit, we found that cyclin B1-associated cdk1 underwent transient inhibitory phosphorylation at tyr-15 and that cyclin B1-cdk1 activity fell more rapidly than the cyclin B1 content. Inhibitory phosphorylation of MPF correlated with phosphorylation changes of cdc25C, the MPF phosphatase, and physical interaction of cdk1 with wee1, the MPF kinase, during M-phase exit. MPF down-regulation required Ca(++)/calmodulin-dependent kinase II (CaMKII) and cAMP-dependent protein kinase (PKA) activities at meiosis and mitosis exit, respectively. Treatment of M-phase extracts with a mutant cyclin B1-cdk1AF complex, refractory to inhibition by phosphorylation, impaired binding of the Anaphase Promoting Complex/Cyclosome (APC/C) to its co-activator Cdc20 and altered M-phase exit. Thus, timely M-phase exit requires a tight coupling of proteolysis-dependent and proteolysis-independent mechanisms of MPF inactivation.
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PMID:Role for non-proteolytic control of M-phase-promoting factor activity at M-phase exit. 1732 11