Control of the ATP, Mg-Dependent Protein Phosphatase by Heat-Stable Regulatory Proteins

Protein Phosphatases Involved in Glycogen Metabolism. Covalent modifications are involved in the control of almost every type of cellular regulation, and the phosphorylation–dephosphorylation cycle appears to be the most prevalent among them. This type of regulation has assumed increasing importance not only in exploring enzyme regulation but also in the study of the signal transfer by receptors, muscular contraction, membrane transport systems, and by the observation that gene products of certain oncogenic viruses display protein kinase activity. The mode of action and regulation of a substantial number of protein kinases is well documented while development in the field of protein phosphatases, which has been reviewed in detail (1–4), is much more recent. This is probably so, because their activity and specificity is basically the result of the interaction of several regulatory proteins and because of the problems involved in the use of phospho-proteins in screening studies and early purification procedures. Glycogen metabolism has always been an outstanding area in metabolic research resulting in remarkable contributions to the development of enzymology. Protein phosphatases have also been investigated most thoroughly in the regulation of the pathways of glycogen synthesis and glycogenolysis. Dephosphorylation by the ATP, Mg-dependent protein phosphatase of all the phosphoproteins known to be relevant in the regulation of glycogen metabolism (Fig. 1) and the activation of this phosphatase by kinase FA have been reviewed recently (3, 4). A Ca2+-calmodulin-dependent protein phosphatase that appears to be identical with calcineurin (5, 6) is present at high concentrations in brain and skeletal muscle but its concentration in liver (7) and vascular smooth muscle (E. Waelkens, J. Goris, and W. Merlevede, unpublished observations) is low. The Ca2+-calmodulin-dependent phosphatase could promote glycogen synthesis through dephosphorylation of inhibitor-1 although this proposal is not easy to reconcile with the role of Ca2+ in muscular contraction.