Phosphorylase kinase mediating the effects of cyclic AMP in muscle

Abstract

In the classic view of the control of phosphorylase b to a conversion by catecholamines, cyclic AMP acts as the second messenger stimulating the activity of cyclic AMP-dependent protein kinase to covalently modify phosphorylase kinase. Phosphorylation of phosphorylase kinase converts this enzyme form with a nonactivated to an activated form with a markedly higher activity at pH 7. There is now considerable evidence that the activity of phospphorylase kinase is also regulated by changeds in the Ca-2+ concentration. The activity of both nonactivated and activated phosphorylase kinase is stimulated by Ca-2+ in the range of concentrations that have been reported to occur in the sacroplasm of contracting muscle, with the activated pphosphorylase kinase having a lower K-alpha for Ca-2+. Thus there are at leaset two mechanisms for the regulation of phosphorylase kinase activity in muscle. These mechanisms may act independently or in concert in controlling glycogenolysis stimulated by catecholamines, anoxia, or tetanic electrical stimulation...