Dunkley P R
Neuroscience Group, Faculty of Medicine, University of Newcastle, NSW, Australia.
Mol Neurobiol. 1991;5(2-4):179-202. doi: 10.1007/BF02935545.
A unique feature of neuronal calcium/calmodulin-stimulated protein kinase II (CaM-PK II) is its autophosphorylation. A number of sites are involved and, depending on the in vitro conditions used, three serine and six threonine residues have been tentatively identified as autophosphorylation sites in the alpha subunit. These sites fall into three categories. Primary sites are phosphorylated in the presence of calcium and calmodulin, but under limiting conditions of temperature, ATP, Mg2+, or time. Secondary sites are phosphorylated in the presence of calcium and calmodulin under nonlimiting conditions. Autonomous sites are phosphorylated in the absence of calcium and calmodulin after initial phosphorylation of Thr-286. Mechanisms that lead to a decrease in CaM-PK II autophosphorylation include the thermolability of the enzyme and the activity of protein phosphatases. A range of in vitro inhibitors of CaM-PK II autophosphorylation have recently been identified. Autophosphorylation of CaM-PK II leads to a number of consequences in vitro, including generation of autonomous activity and subcellular redistribution, as well as alterations in conformation, activity, calmodulin binding, substrate specificity, and susceptibility to proteolysis. It is established that CaM-PK II is autophos-phorylated in neuronal cells under basal conditions. Depolarization and/or activation of receptors that lead to an increase in intracellular calcium induces a marked rise in the autophosphorylation of CaM-PK II in situ. The incorporation of phosphate is mainly found on Thr-286, but other sites are also phosphorylated at a slower rate. One consequence of the increase in CaM-PK II autophosphorylation in situ is an increase in the level of autonomous kinase activity. It is proposed that the formation of an autonomous enzyme is only one of the consequences of CaM-PK II autophosphorylation in situ and that some of the other consequences observed in vitro will also be seen. CaM-PK II is involved in the control of neuronal plasticity, including neurotransmitter release and long-term modulation of postreceptor events. In order to understand the function of CaM-PK II, it will be essential to ascertain more fully the mechanisms of its autophosphorylation in situ, including especially the sites involved, the consequences of this autophosphorylation for the kinase activity, and the relationships between the state of CaM-PK II autophosphorylation and the physiological events within neurons.
神经元钙/钙调蛋白依赖性蛋白激酶II（CaM-PK II）的一个独特特征是其自身磷酸化。涉及多个位点，根据所使用的体外条件，已初步确定α亚基中的三个丝氨酸和六个苏氨酸残基为自身磷酸化位点。这些位点可分为三类。初级位点在有钙和钙调蛋白存在的情况下被磷酸化，但在温度、ATP、Mg2+或时间的限制条件下。次级位点在无限制条件下有钙和钙调蛋白存在时被磷酸化。自主位点在Thr-286初始磷酸化后在无钙和钙调蛋白的情况下被磷酸化。导致CaM-PK II自身磷酸化减少的机制包括该酶的热不稳定性和蛋白磷酸酶的活性。最近已鉴定出一系列CaM-PK II自身磷酸化的体外抑制剂。CaM-PK II的自身磷酸化在体外会导致多种结果，包括自主活性的产生和亚细胞重新分布，以及构象、活性、钙调蛋白结合、底物特异性和对蛋白水解敏感性的改变。已确定CaM-PK II在基础条件下在神经元细胞中会发生自身磷酸化。导致细胞内钙增加的受体去极化和/或激活会诱导原位CaM-PK II的自身磷酸化显著增加。磷酸盐的掺入主要见于Thr-286，但其他位点也会以较慢的速率被磷酸化。原位CaM-PK II自身磷酸化增加的一个结果是自主激酶活性水平的增加。有人提出，自主酶的形成只是原位CaM-PK II自身磷酸化的结果之一，并且在体外观察到的一些其他结果也会出现。CaM-PK II参与神经元可塑性的控制，包括神经递质释放和受体后事件的长期调节。为了理解CaM-PK II的功能，更全面地确定其原位自身磷酸化的机制至关重要，特别是涉及的位点、这种自身磷酸化对激酶活性的影响，以及CaM-PK II自身磷酸化状态与神经元内生理事件之间的关系。
