Phosphorylation by casein kinase II alters the biological activity of calmodulin.
Phosphorylation by casein kinase II alters the biological activity of calmodulin.
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DOI：
10.1042/bj2830021
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发表时间：
1992-04
期刊：
影响因子：
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通讯作者：
D. Sacks;H. Davis;J. Williams;E. Sheehan;J. Garcia;J. McDonald
中科院分区：
文献类型：
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作者：
D. Sacks;H. Davis;J. Williams;E. Sheehan;J. Garcia;J. McDonald
钙调蛋白是细胞内主要的钙结合蛋白，为许多细胞内酶提供钙依赖的调节。钙调蛋白的磷酸化可能为调节其作为信号转导的功能提供了另一种机制。磷酸钙调蛋白在组织和细胞中已被鉴定，钙调素在体外和完整细胞中都被各种酶磷酸化。酪蛋白激酶II使丝氨酸/苏氨酸残基上的钙调蛋白磷酸化，降低了其激活肌球蛋白轻链激酶和环核苷酸磷酸二酯酶的能力。对于肌球蛋白轻链激酶，其主要作用是抑制Vmax。钙离子或钙调素达到半最大反应速度的浓度(K0.5)没有明显变化。相反，对于磷酸二酯酶，钙调蛋白的磷酸化显著增加了钙调蛋白的K0.5，而不显著改变Vmax。或钙离子的K0.5。钙调蛋白磷酸化的化学计量比越高，对两种酶的钙调蛋白刺激活性的抑制就越大。因此，酪蛋白激酶II对钙调蛋白的磷酸化似乎提供了一种钙非依赖性的机制，通过该机制，钙调蛋白至少调节两个重要的靶酶，即肌球蛋白轻链激酶和环核苷酸磷酸二酯酶。
Calmodulin is the major intracellular Ca(2+)-binding protein, providing Ca(2+)-dependent regulation of numerous intracellular enzymes. The phosphorylation of calmodulin may provide an additional mechanism for modulating its function as a signal transducer. Phosphocalmodulin has been identified in tissues and cells, and calmodulin is phosphorylated both in vitro and in intact cells by various enzymes. Phosphorylation of calmodulin on serine/threonine residues by casein kinase II decreases its ability to activate both myosin-light-chain kinase and cyclic nucleotide phosphodiesterase. For myosin-light-chain kinase the primary effect is an inhibition of the Vmax. of the reaction, with no apparent change in the concentration at which half-maximal velocity is attained (K0.5) for either Ca2+ or calmodulin. In contrast, for phosphodiesterase, phosphorylation of calmodulin significantly increases the K0.5 for calmodulin without noticeably altering the Vmax. or the K0.5 for Ca2+. The higher the stoichiometry of phosphorylation of calmodulin, the greater the inhibition of calmodulin-stimulated activity for both enzymes. Therefore the phosphorylation of calmodulin by casein kinase II appears to provide a Ca(2+)-independent mechanism whereby calmodulin regulates at least two important target enzymes, myosin-light-chain kinase and cyclic nucleotide phosphodiesterase.