Elucidation of the mechanism of biomineralization with acidic phosphoprotein from molecular evolution studies

牙本质基质蛋白1(DMP1)，是构成骨的酸性磷蛋白之一。DMP1的分子进化研究表明，酪蛋白激酶（CK）的磷酸化可能与DMP1的功能有关。被CK高度磷酸化的DMP1具有大量的酸性结构域。由于DMP1的高酸性，人们认为带负电荷的DMP1可以与钙结合，从而调节基质矿化。在本研究中，我们发现DMP1的丝氨酸残基在骨和培养的成骨细胞中被磷酸化，成骨细胞来源的CK可能使DMP1磷酸化。CK抑制剂的培养实验表明，矿化是通过抑制CK活性来控制的。因此，我们推测DMP1何时被CK磷酸化，带负电荷的DMP1是否促进矿化。

Dentin matrix protein 1(DMP1), which is a one of the acidic phosphoproteins composed of the bone. Molecular evolution study of DMP1 indicated that phosphorylation by casein kinase(CK) might be related to the DMP1 function. Highly phosphorylated DMP1 by CK has a large number of acidic domains. Because of its highly acidic nature, it is supposed that negative-charged DMP1 can bind to calcium, thereby regulating matrix mineralization. In this study, we found that Ser residues of DMP1 were phosphorylated in the bone and cultured osteoblast and that osteoblast-derived CK might phosphorylate DMP1. Culture experiment with CK inhibitor indicated that mineralization was controlled by inhibition of the CK activity. Therefore, it was supposed when DMP1 was phosphorylated by CK, and did negative-charged DMP1 promoted mineralization.