Yanagihara N, Tachikawa E, Izumi F, Yasugawa S, Yamamoto H, Miyamoto E
Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
J Neurochem. 1991 Jan;56(1):294-8. doi: 10.1111/j.1471-4159.1991.tb02595.x.
We investigated the effect of staurosporine on Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) purified from rat brain. (a) Staurosporine (10-100 nM) inhibited the activity of CaM kinase II. The half-maximal and maximal inhibitory concentrations were 20 and 100 nM, respectively. (b) The inhibition with staurosporine was of the noncompetitive type with respect to ATP, calmodulin, and phosphate acceptor (beta-casein). (c) Staurosporine suppressed the auto-phosphorylation of alpha- and beta-subunits of CaM kinase II at concentrations similar to those at which the enzyme activity was inhibited. (d) Staurosporine also attenuated the Ca2+/calmodulin-independent activity of the autophosphorylated CaM kinase II. These results suggest that staurosporine inhibits CaM kinase II by interacting with the catalytic domain, distinct from the ATP-binding site or substrate-binding site, of the enzyme and that staurosporine is an effective inhibitor for CaM kinase II in the cell system.
我们研究了星形孢菌素对从大鼠脑中纯化的钙/钙调蛋白依赖性蛋白激酶II（CaM激酶II）的作用。（a）星形孢菌素（10 - 100 nM）抑制CaM激酶II的活性。半最大抑制浓度和最大抑制浓度分别为20 nM和100 nM。（b）就ATP、钙调蛋白和磷酸受体（β-酪蛋白）而言，星形孢菌素的抑制作用属于非竞争性类型。（c）星形孢菌素在与抑制酶活性相似的浓度下抑制CaM激酶II的α和β亚基的自磷酸化。（d）星形孢菌素还减弱了自磷酸化的CaM激酶II的钙/钙调蛋白非依赖性活性。这些结果表明，星形孢菌素通过与该酶不同于ATP结合位点或底物结合位点的催化结构域相互作用来抑制CaM激酶II，并且星形孢菌素在细胞系统中是CaM激酶II的有效抑制剂。
