Activation of glycogen phosphorylase kinase by a calcium-activated, cyclic nucleotide-independent protein kinase system.

Abstract

A protein kinase, which was produced from its proenzyme occurring in rat brain upon limited proteolysis by a Ca2+-dependent protease from the same tissue (Inoue, M., Kishimoto, A., Takai, Y., and Nishizlka, Y. (1977) J. Biol. Chem. 252, 7610-7616, was capable of phosphorylating alpha and beta subunits of rabbit skeletal muscle glycogen phosphorylase kinase, resulting in a marked enhancement of the enzymatic activity. This protein kinase was entirely independent of cyclic nucleotides and differed from the catalytic subunit of cyclic AMP-dependent protein kinase. The activation of phosphorylase kinase by this active protein kinase was not inhibited by a protein inhibitor of cyclic AMP-dependent protein kinase, nor by ethylene glycol bis(beta-aminoethyl ether)N',N'-tetraacetic acid, which prevented autophosphorylation of phosphorylase kinase. The proenzyme was distinguishable from cyclic nucleotide-dependent protein kinases, since it did not bind cyclic AMP and cyclic GMP, and was inactive in the phosphorylation and activation of phosphorylase kinase both in the presence and absence of these cyclic nucleotides. Neither the protein kinase nor its proenzyme showed phosphorylase kinase activity. Available evidence indicates that the Ca2+-activated, cyclic nucleotide-independent protein kinase system as well as cyclic AMP-dependent protein kinase shows an ability to stimulate glycogen breakdown as far as tested in vitro.