权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Structure and Function of Calmodulin-dependent Protein Kinase II and Its Physiological Significance

钙调蛋白依赖性蛋白激酶II的结构、功能及其生理意义

基本信息

批准号：
01440023
负责人：
FUJISAWA Hitoshi
金额：
$ 17.98万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

Four different polypeptides (isoforms) of calmodulin-dependent protein kinase II (CaM-kinase II), alpha, beta, gamma, and delta, which derived from four different genes, were revealed by cDNA sequence analysis of the rat brain extract. RNA blot bybridization analysis of the extracts from various tissues with probes specific for the respective mRNAs showed that gamma and delta mRNAs were expressed in various tissues, while alpha and beta mRNAs were primarily, if not exclusively, expressed in brain.Autophosphorylation of CaM-kinase II is thought to be an important selfregulatory mechanism for controlling its protein kinase activity. The enzyme that had not undergone autophosphorylation exhibited only 15% of the maximum activity even in the presence of Ca^<2+>/calmodulin, but exposure of the enzyme to Ca^<2+>/calmodulin caused rapid autophosphorylation of the enzyme on Thr^<286>, thereby converting the enzyme to the most active form. The active form had the protein kinase activity even in … More the absence of Ca^<2+>/calmodulin, although the affinity for the protein substrates were much lower in the absence of Ca^<2+> than in its presence.Tyrosine hydroxylase catalyzing the rate-limiting step in the biosynthesis of catecholamines is known to be phosphorylated by three second messenger-responsive multifunctional protein kinases, cAMP-dependent protein kinase (A-kinase), protein kinase C (C-kinase), and CaM-kinase II. However, the enzyme was activated via phosphorylation by A-kinase, not acivated by C-kinase, and activated only in the presence of activator protein by CaM-kinase II. The possible regulatory mechanism of the enzyme activity by these three multifunctional protein kinases were suggested.Another calmodulin-dependent protein kinase occurring almost exclusively in brain, calmodulin-dependent protein kinase IV (CaM-kinase IV), was found to show a broad substrate specificity, suggesting its physiological significance in the regulation of the brain function by Ca^<2+>.Interestingly, CaM-kinase IV was activated by autophosphorylation but inactivated via phosphorylation by A-kinase. Less

通过对大鼠脑提取物的cDNA序列分析，揭示了钙调蛋白依赖性蛋白激酶II（CaM-激酶II）的四种不同多肽（亚型），α，β，γ和δ，它们来自四种不同的基因。RNA印迹杂交分析的提取物从不同的组织与探针特异性各自的mRNA表明，γ和δ mRNA表达在各种组织中，而α和β mRNA的主要，如果不是唯一的，在brain.Autophosphorylation的钙调蛋白激酶II被认为是一个重要的自我调节机制，控制其蛋白激酶活性。即使在Ca ^2 +/钙调蛋白存在的情况下，未发生自磷酸化的酶也仅表现出最大活性的15%，但将酶暴露于Ca ^2 +/钙调蛋白中会导致Thr ^上的酶快速自磷酸化，从而将酶转化为最具活性的形式。<286>活性形式具有蛋白激酶活性，即使在 ...更多信息酪氨酸羟化酶是催化儿茶酚胺生物合成的限速酶，已知它被三种第二信使应答性多功能蛋白激酶磷酸化，cAMP依赖性蛋白激酶，（A-激酶）、蛋白激酶C（C-激酶）和CaM-激酶II。然而，该酶被激活通过磷酸化的A-激酶，不活化的C-激酶，激活的激活蛋白的存在下，由钙调蛋白激酶II。另一种钙调素依赖性蛋白激酶IV几乎只存在于脑中，它是钙调素依赖性蛋白激酶IV（CaM-激酶IV）显示出广泛的底物特异性，表明其在Ca ^2+调节脑功能中的生理意义。有趣的是，钙调蛋白激酶IV通过自身磷酸化激活，但通过A激酶磷酸化失活。少