Multiple Ca2+-calmodulin-dependent protein kinase kinases from rat brain - Purification, regulation by Ca2+-calmodulin, and partial amino acid sequence
Multiple Ca2+-calmodulin-dependent protein kinase kinases from rat brain - Purification, regulation by Ca2+-calmodulin, and partial amino acid sequence
复制标题
DOI：
10.1074/jbc.271.18.10806
复制
发表时间：
1996-05-03
影响因子：
4.8
通讯作者：
Kemp, BE
中科院分区：
文献类型：
--
作者：
Edelman, AM;Mitchelhill, KI;Kemp, BE
我们从大鼠脑中纯化了两种钙调蛋白依赖性蛋白激酶I（CaM激酶I）激活激酶，称为CaM激酶I激酶-α和CaM激酶I激酶-β（分别为CaMKIK α和CaMKIK β）。CaMKIK α和CaMKIK β也能够激活CaM激酶IV。CaM激酶I和CaM激酶IV的激活分别通过两种激酶Thr-177和Thr-196的“激活环”区域内的等效Thr残基的磷酸化而发生。CaMKIK α和CaMKIK β的活性本身受到Ca 2 +-CaM的强烈刺激，并且两者似乎都能够进行Ca 2 +-CaM依赖性自磷酸化。纯化的酶的自动微序列分析确定CaMKIK α和β是不同基因的产物。除了大鼠，对应于这些CaM激酶激酶的同源核酸存在于人类和线虫秀丽隐杆线虫中。因此，CaMKIK α和CaMKIK β是一个酶家族的代表，其可以在多种真核生物中作为Ca 2 +-CaM驱动的信号转导级联的关键中间体发挥作用。
We have purified to near homogeneity from rat brain two Ca2+-calmodulin-dependent protein kinase I (CaM kinase I) activating kinases, termed here CaM kinase I kinase-alpha and CaM kinase I kinase-beta (CaMKIK alpha and CaMKIK beta, respectively). Both CaMKIK alpha and CaMKIK beta are also capable of activating CaM kinase IV, Activation of CaM kinase I and CaM kinase TV occurs via phosphorylation of an equivalent Thr residue within the ''activation loop'' region of both kinases, Thr-177 and Thr-196, respectively. The activities of CaMKIK alpha and CaMKIK beta are themselves strongly stimulated by the presence of Ca2+-CaM, and both appear to be capable of Ca2+-CaM-dependent autophosphorylation. Automated microsequence analysis of the purified enzymes established that CaMKIK alpha and -beta are the products of distinct genes, In addition to rat, homologous nucleic acids corresponding to these CaM kinase kinases are present in humans and the nematode, Caenorhabditis elegans. CaMKIK alpha and CaMKIK beta are thus representatives of a family of enzymes, which may function as key intermediaries in Ca2+-CaM-driven signal transduction cascades in a wide variety of eukaryotic organisms.