Calcium control of muscle phosphorylase kinase through the combined action of calmodulin and troponin.
Although it has been believed for several years that Ca2+ are the means by which glycogenolysis and muscle contraction are synchronized, it is only over the past two years that this concept has started to be placed on a firm molecular basis. The current evidence suggests that the regulation of phosphorylase kinase by Ca2+ in vivo is achieved through the interaction of this divalent cation with calmodulin (the delta subunit) and troponin C, and that the relative importance of these two calcium binding proteins depends on the state of phosphorylation of the enzyme [FIGURE 1]. In the low-activity dephosphorylated b form, increasing Ca2+ from 0.1 microM to concentrations in the microM range produces a 5-10-fold activation through the binding of Ca2+ to the delta subunit, and a further 15-25-fold activation through the binding of Ca2+ to troponin C [TABLE 1]. Troponin C rather than the delta subunit is therefore the dominant calcium dependent regulator of the b form, providing an attractive mechanism for coupling glycogenolysis and muscle contraction. On the other hand, the high-activity phosphorylated a form is only activated very slightly by troponin [Section 7]. The delta subunit is therefore the dominant calcium dependent regulator of the hormonally activated state of the enzyme. It has recently become clear that phosphorylase kinase not only phosphorylates and activates phosphorylase, but also phosphorylates glycogen synthase, decreasing its activity. The regulation of phosphorylase kinase by Ca2+ may therefore also provide a mechanism for achieving synchronous control of the pathways of glycogenolysis and glycogen synthesis.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002147:Calmodulin / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology*; D010764:Phosphorylase Kinase / Q000378:metabolism*; D011485:Protein Binding; D014336:Troponin / Q000378:metabolism*; D019209:Troponin C
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D046911:Macromolecular Substances; D009124:Muscle Proteins; D014336:Troponin; D019209:Troponin C; D010764:Phosphorylase Kinase; D002118:Calcium