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Signal Transduction Mediated by Multifunctional Ca^<2+>/calmodulin-dependent Protein Kinases

多功能Ca^2/钙调蛋白依赖性蛋白激酶介导的信号转导

基本信息

批准号：
10102002
负责人：
FUJISAWA Hitoshi
金额：
$ 137.6万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Specially Promoted Research
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10102002/
关键词：
Calcium ion Calmodulin CaM-kinase cascade CaM-kinase II CaM-kinase IV CaM kinase kinase CaM-kinase phosphatase CaM-kinase phosphatase N Aキナーゼ CaMキナーゼI シグナル伝達蛋白質リン酸化酵素蛋白質脱リン酸化酵素

项目摘要

1. Regulation of CaM-kinase IICa^<2+>/calmodulin-dependent protein kinase (CaM-kinase) II is activated through autophosphorylation of Thr-286. We purified a new protein phosphatase (named CaM-kinase phosphatase), which dephosphorylates the phosphorylated Thr-286 restoring the activated CaM-kinase II to its original state, from rat brain and studied the properties of CaM-kinase phosphatase.The binding affinity for calmodulin of CaM-kinase II was studied using surface plasmon resonance. The dissociation rate constant of CaM-kinase II for calmodulin was decreased upon autophosphorylation of Thr-286 by approximately 10, 000-fold, suggesting that CaM-kinase II, once activated, can keep calmodulin even in the presence of many calmodulin-binding proteins. Thus, CaM-kinase II, once activated, may keep the highest activity in the cell until cytosolic Ca^<2+> is completely pumped out of the cell.2. Regulation of CaM-kinases IV and ICaM-kinases IV and I which have been activated upon phosphorylat … More ion of Thr-196 and Thr-177, respectively, by an upstream CaM-kinase kinase were deactivated by incubation with CaM-kinase phosphatase. CaM-kinase phosphatase specifically dephosphorylated phosphorylated Thr-286, Thr-196, and Thr-177 of CaM-kinases II, IV, and I, respectively. Thus, the activities of the three multifunctional CaM-kinases, such as CaM-kinases I, II, and IV, are all regulated by phosphorylation and dephosphorylation catalyzed by a specific protein kinase and phosphatase.3. Identification of CaM-kinase phosphatase NA protein (named CaM-kinase phosphatase N) showing a sequence homology to CaM-kinase phosphatase was found by a database search. CaM-kinase phosphatase N has a substrate specificity and other catalytic properties very similar to those of CaM-kinase phosphatase. However, CaM-kinase phosphatase is distributed in the cytosol but CaM-kinase phosphatase N is distributed in the cell nuclei.4. Possible model for CaM-kinase cascadeOn the basis of the results that tissue and subcellular distributions of CaM-kinases, CaM-kinase kinases, and CaM-kinase phosphatases were examined, a possible model for CaM-kinase cascade was proposed. Less

1.钙调蛋白依赖性蛋白激酶（CaM-激酶）II的调节通过Thr-286的自磷酸化被激活。我们从大鼠脑中纯化了一种新的蛋白磷酸酶（CaM-kinase phosphatase，简称CaM-K），它能使磷酸化的Thr-286去磷酸化，使活化的CaM-K恢复到原来的状态，并研究了CaM-K的性质，用表面等离子体共振技术研究了CaM-K与钙调素的结合能力。CaM-激酶II对钙调蛋白的解离速率常数在Thr-286的自磷酸化后降低约10，000倍，表明CaM-激酶II一旦被激活，即使在许多钙调蛋白结合蛋白存在下也能保持钙调蛋白。因此，CaM激酶II一旦被激活，就可以在细胞中保持最高活性，直到胞质Ca^2+被完全泵出细胞。磷酸化激活的CaM激酶IV和ICaM激酶IV和I的调节 ...更多信息通过与CaM-激酶磷酸酶温育，使上游CaM-激酶分别对Thr-196和Thr-177离子失活。CaM激酶磷酸酶特异性去磷酸化CaM激酶II、IV和I的磷酸化Thr-286、Thr-196和Thr-177。因此，这三种多功能的钙调素激酶，如钙调素激酶I、II和IV的活性都是由特定的蛋白激酶和磷酸酶催化磷酸化和去磷酸化来调节的.通过数据库检索发现了与CaM激酶磷酸酶具有序列同源性的CaM激酶磷酸酶NA蛋白（命名为CaM激酶磷酸酶N）。CaM-激酶磷酸酶N具有与CaM-激酶磷酸酶非常相似的底物特异性和其它催化性质。而CaM-激酶磷酸酶分布在胞浆中，而CaM-激酶磷酸酶N则分布在细胞核中. CaM-激酶级联反应的可能模型根据对CaM-激酶、CaM-激酶激酶和CaM-激酶磷酸酶的组织和亚细胞分布的研究结果，提出了CaM-激酶级联反应的可能模型。少