Activation of phosphorylase kinase from rabbit skeletal muscle by calmodulin and troponin

Phosphorylase kinase is of central importance in the nervous and hormonal control of glycogenolysis in mammalian skeletal muscle, since its activity is dependent on Ca*’ and stimulated by a phosphoryla- tion reaction catalysed by cyclic AMP-dependent protein kinase [ I]. Phosphorylase kinase from mammalian skeletal muscle has mol. wt 1 280 000 and possesses the struc- ture (@y8)4 where the o- and P-subunits are the components phosphorylated by cyclic AMP-dependent protein kinase [I] and the s-subunit is identical to the calcium binding protein termed calmodulin [2,3]. Calmodulin, formerly termed the modulator protein or calcium-dependent regulator protein, was originally identified as a factor which stimulated the activity of the high Km cyclic nucleotide phosphodiesterase of brain tissue [4,5] but it has subsequently been impli- cated in the control of a variety of intracellular processes which are regulated by Ca*’ [6-l 11. Calmodulin binds 4 Ca*‘/mol [ 121 and the calcium binding properties of phosphorylase kinase [ 131 support the view that all the high affinity binding sites for calcium are located on the 6-subunit [3]. This in turn suggests that the 6 -subunit is the compo- nent which confers calcium sensitivity to phosphorylase