Edman C F, George S E, Means A R, Schulman H, Yaswen P
Life Sciences Division, Lawrence Berkeley Laboratory, CA 94720.
Eur J Biochem. 1994 Dec 1;226(2):725-30. doi: 10.1111/j.1432-1033.1994.tb20101.x.
A calmodulin-like protein, which is identical in size and 85% identical to vertebrate calmodulin, was recently identified by 'subtractive hybridization' comparison of transcripts expressed in normal versus transformed human mammary epithelial cells. Unlike the ubiquitous distribution of calmodulin, calmodulin-like protein expression is restricted to certain epithelial cells, and appears to be modulated during differentiation. In addition, calmodulin-like protein levels are often significantly reduced in malignant tumor cells as compared to corresponding normal epithelial cells. The current studies compare calmodulin-like protein functions with those of calmodulin. We find that calmodulin-like protein activation of multifunctional Ca2+/calmodulin-dependent protein kinase II (calmodulin kinase II) is equivalent to activation by calmodulin, but that four other calmodulin-dependent enzymes, cGMP phosphodiesterase, calcineurin, nitric-oxide synthase, and myosin-light-chain kinase, display much weaker activation by calmodulin-like protein than by calmodulin. In the case of myosin-light-chain kinase, calmodulin-like protein competitively inhibits calmodulin activation of the enzyme with a Ki value of 170 nM. Thus, calmodulin-like protein may have evolved to function as a specific agonist of certain calmodulin-dependent enzymes, and/or as a specific competitive antagonist of other calmodulin-dependent enzymes.
最近，通过对正常和转化的人乳腺上皮细胞中表达的转录本进行“消减杂交”比较，鉴定出一种大小与脊椎动物钙调蛋白相同且85%同源的类钙调蛋白。与钙调蛋白的广泛分布不同，类钙调蛋白的表达仅限于某些上皮细胞，并且在分化过程中似乎受到调控。此外，与相应的正常上皮细胞相比，恶性肿瘤细胞中的类钙调蛋白水平通常会显著降低。目前的研究比较了类钙调蛋白与钙调蛋白的功能。我们发现，类钙调蛋白对多功能Ca2+/钙调蛋白依赖性蛋白激酶II（钙调蛋白激酶II）的激活作用与钙调蛋白相当，但其他四种钙调蛋白依赖性酶，即cGMP磷酸二酯酶、钙调神经磷酸酶、一氧化氮合酶和肌球蛋白轻链激酶，类钙调蛋白对它们的激活作用比对钙调蛋白弱得多。就肌球蛋白轻链激酶而言，类钙调蛋白竞争性抑制该酶的钙调蛋白激活，Ki值为170 nM。因此，类钙调蛋白可能已经进化为某些钙调蛋白依赖性酶的特异性激动剂，和/或其他钙调蛋白依赖性酶的特异性竞争性拮抗剂。
