Characterization of a Ca2+/Calmodulin-dependent Protein Kinase Cascade

Characterization of a Ca2+/Calmodulin-dependent Protein Kinase Cascade
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Ca2/钙调蛋白依赖性蛋白激酶级联的表征

DOI:
--
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发表时间:
1995
影响因子:
4.8
通讯作者:
T. Soderling
T. Soderling
中科院分区:
生物学2区
文献类型:
--
作者:
H. Tokumitsu;T. Soderling

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最近的研究表明,Ca2+/钙调蛋白依赖性蛋白激酶 IV (CaM-kinase IV) 可以通过转录激活蛋白的磷酸化介导 Ca2+ 依赖性基因表达调节。我们之前已经鉴定并纯化了一种 68-kDa 大鼠脑 CaM 激酶激酶,该激酶磷酸化并增加 CaM 激酶 IV 的总活性和 Ca2+ 独立活性(Tokumitsu, H.、Brickey, D. A.、Gold, J.、Hidaka, H.、Sikela, J. 和 Soderling, T. R.(1994) J. Biol. Chem. 269, 28640-28647)。使用纯化的脑激酶的部分氨基酸序列,从大鼠脑cDNA文库中克隆CaM激酶激酶cDNA。 Northern 印迹分析显示 CaM 激酶激酶 mRNA(3.4 KB)在大鼠脑、胸腺和脾脏中表达。序列分析显示,该cDNA编码一个505个氨基酸的蛋白质,该蛋白质含有共有蛋白激酶基序,并且与CaM激酶家族成员有30-40%的同源性。 COS-7 细胞中 cDNA 的表达产生了明显的 68 kDa CaM 结合蛋白,该蛋白在 Mg2+/ATP 和 Ca2+/CaM 存在的情况下催化 CaM 激酶 I 和 IV 的体外激活,但不催化 CaM 激酶 II 的激活。与单独的 CaM 激酶 IV 相比,CaM 激酶激酶与 CaM 激酶 IV 的共表达使 cAMP 反应元件结合蛋白依赖性基因表达增强了 14 倍。这些结果与 CaM 激酶 I 和 IV 通过涉及 CaM 激酶激酶的独特信号转导级联进行调节的假设一致。
Recent studies have demonstrated that Ca2+/calmodulin-dependent protein kinase IV (CaM-kinase IV) can mediate Ca2+-dependent regulation of gene expression through the phosphorylation of transcriptional activating proteins. We have previously identified and purified a 68-kDa rat brain CaM-kinase kinase that phosphorylates and increases total and Ca2+-independent activities of CaM-kinase IV (Tokumitsu, H., Brickey, D. A., Gold, J., Hidaka, H., Sikela, J., and Soderling, T. R.(1994) J. Biol. Chem. 269, 28640-28647). Using a partial amino acid sequence of the purified brain kinase, a CaM-kinase kinase cDNA was cloned from a rat brain cDNA library. Northern blot analysis showed that CaM-kinase kinase mRNA (3.4 kilobases) was expressed in rat brain, thymus, and spleen. Sequence analyses revealed that the cDNA encoded a 505-amino acid protein, which contained consensus protein kinase motifs and was 30-40% homologous with members of the CaM-kinase family. Expression of the cDNA in COS-7 cells yielded an apparent 68-kDa CaM-binding protein, which catalyzed in vitro activation in the presence of Mg2+/ATP and Ca2+/CaM of CaM-kinases I and IV but not of CaM-kinase II. Co-expression of CaM-kinase kinase with CaM-kinase IV gave a 14-fold enhancement of cAMP-response element-binding protein-dependent gene expression compared with CaM-kinase IV alone. These results are consistent with the hypothesis that CaM-kinases I and IV are regulated through a unique signal transduction cascade involving CaM-kinase kinase.
DOI: --
发表时间: 1994
期刊: The Journal of biological chemistry
影响因子: --
作者:
Enslen,H;Sun,P;Brickey,D;Soderling,SH;Klamo,E;Soderling,TR
通讯作者: Soderling,TR
Ca(2)-钙调蛋白依赖性蛋白激酶 Ia 的蛋白激活剂。
DOI: --
发表时间: 1994
期刊: The Journal of biological chemistry
影响因子: --
作者:
Lee,JC;Edelman,AM
通讯作者: Edelman,AM
钙/钙调蛋白依赖性蛋白激酶 II。
DOI: 10.1016/b978-0-12-152831-7.50007-x
发表时间: 1990
期刊: Current topics in cellular regulation
影响因子: --
作者:
Colbran,RJ;Soderling,TR
通讯作者: Soderling,TR
囊性纤维化跨膜电导调节因子的磷酸化。
DOI: --
发表时间: 1992
期刊: The Journal of biological chemistry
影响因子: --
作者:
Picciotto,MR;Cohn,JA;Bertuzzi,G;Greengard,P;Nairn,AC
通讯作者: Nairn,AC
DOI: 10.1073/pnas.88.7.2850
发表时间: 1991-04-01
影响因子: 11.1
作者:
JENSEN, KF;OHMSTEDE, CA;SAHYOUN, N
通讯作者: SAHYOUN, N