Sivaramakrishnan S, Vandenheede J R, Merlevede W
Adv Enzyme Regul. 1983;21:321-30. doi: 10.1016/0065-2571(83)90021-3.
Amongst the several cyclic AMP-and Ca2+-independent synthase kinases that are reported by several laboratories, the kinase FA is unique in having a bifunctional nature: it can also promote the conversion of the inactive ATP,Mg-dependent protein phosphatase to its active form. By doing so, it produces an active multisubstrate phosphatase which reverses the major protein phosphorylations that control glycogen metabolism. In rabbit skeletal muscle, two forms of kinase FA can be distinguished, which seem to interconvert into one common bifunctional catalytic unit. It is proposed that the two molecular forms either reflect the existence of a regulatory subunit which dissociates during the purification, or suggest a reversible modification of the bifunctional catalytic unit. In order to serve a useful physiological role in the regulation of glycogen metabolism, the enzyme has to select between its two opposite activities in any given physiological condition, and the putative regulatory subunit or modification of the catalytic unit could play a fundamental role in this modulation. In vitro experiments have provided us with two proteins that are suitable candidates to discriminate between the two activities in FA: the heat stable phosphatase inhibitor-1 and the phosphatase modulator protein. Both can prevent the expression of the protein phosphatase activity; however, a well defined amount of modulator protein is absolutely required for an efficient activation of the FC-enzyme by FA, but an excess [M] decreases the rate as well as the extent of activation. This means that excess modulator protein can block the phosphatase activating capacity of FA. The same, or even higher, concentrations of modulator (or inhibitor-1) have absolutely no effect on the synthase kinase activity of the FA protein. No effector of this synthase kinase activity has yet been found, although by its shunting away from the phosphatase activation, more of the FA could be effective as a synthase kinase.
在多个实验室报道的几种不依赖环磷酸腺苷和钙离子的合酶激酶中，激酶FA具有独特的双功能性质：它还能促进无活性的ATP、镁依赖性蛋白磷酸酶转变为其活性形式。通过这样做，它产生一种活性多底物磷酸酶，该磷酸酶可逆转控制糖原代谢的主要蛋白质磷酸化过程。在兔骨骼肌中，可以区分出两种形式的激酶FA，它们似乎可相互转化为一个共同的双功能催化单元。有人提出，这两种分子形式要么反映了在纯化过程中解离的调节亚基的存在，要么表明双功能催化单元存在可逆修饰。为了在糖原代谢调节中发挥有益的生理作用，该酶必须在任何给定的生理条件下在其两种相反的活性之间进行选择，而假定的调节亚基或催化单元的修饰可能在这种调节中起基本作用。体外实验为我们提供了两种适合区分FA中两种活性的蛋白质：热稳定磷酸酶抑制剂-1和磷酸酶调节蛋白。两者都能阻止蛋白磷酸酶活性的表达；然而，为了使FA有效激活FC酶，绝对需要一定量的调节蛋白，但过量的[M]会降低激活速率和激活程度。这意味着过量的调节蛋白会阻断FA的磷酸酶激活能力。相同浓度甚至更高浓度的调节剂（或抑制剂-1）对FA蛋白的合酶激酶活性绝对没有影响。尽管通过使其不参与磷酸酶激活，更多的FA可能作为合酶激酶发挥作用，但尚未发现这种合酶激酶活性的效应物。
