Fischer E H
Department of Biochemistry, University of Washington, Seattle, USA.
Adv Enzyme Regul. 1999;39:359-69. doi: 10.1016/s0065-2571(98)00014-4.
The above data, and others not described herein, indicate the following: First, that phosphatases are not scavenger enzymes, simply there to remove the phosphate groups introduced by the kinases. They cannot be viewed simply as providing an 'off' switch in an 'on/off' kinase/phosphatase system. Kinases and phosphatases do not carry out one-way and opposing reactions. The same enzyme, depending on where it localizes within the cell, or the molecule with which it might interact, can serve either as a positive or negative determinant in defining cell behavior. In many instances, it can act synergistically with the kinases to enhance the phosphorylation reaction. Second, the factors that determine whether a phosphatase would enhance or oppose a kinase reaction would seem to depend less on its state of activity than on its subcellular localization. This would suggest that if one wanted to call upon it to control transformation, one should try to tamper with its localization segments or whatever binding proteins it might be attached to--rather than with its catalytic domains. Displacement of these enzymes from where they are meant to bind would seem a more promising approach than trying to modulate their catalytic activity. Finally, their architectural features are so basically different from those of the kinases, with receptor tyrosine phosphatases displaying all the structural characteristics of cell adhesion molecules, that they must also have a mission of their own in cell development, survival and death, quite apart from that of the kinases.
首先，磷酸酶并非清除酶，仅仅是用于去除激酶引入的磷酸基团。它们不能简单地被视为在“开/关”激酶/磷酸酶系统中提供“关闭”开关。激酶和磷酸酶并非进行单向且相反的反应。同一种酶，取决于其在细胞内的定位，或者与之相互作用的分子，在定义细胞行为时既可以作为正向决定因素，也可以作为负向决定因素。在许多情况下，它可以与激酶协同作用以增强磷酸化反应。其次，决定磷酸酶是增强还是对抗激酶反应的因素似乎与其活性状态的关系较小，而与其亚细胞定位的关系更大。这表明，如果想要利用它来控制细胞转化，应该尝试干预其定位片段或其可能附着的任何结合蛋白，而不是其催化结构域。将这些酶从其预期结合的位置移位似乎比试图调节其催化活性更具前景。最后，它们的结构特征与激酶的结构特征基本不同，受体酪氨酸磷酸酶展现出细胞黏附分子的所有结构特征，以至于它们在细胞发育、存活和死亡中必定也有自身独特的使命，这与激酶的使命截然不同。
