Advances in enzyme regulation. vol:21 pages:321-30
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.