Phosphorylation and inactivation of rat liver glycogen synthase by cAMP-dependent protein kinase and cAMP-independent synthase (casein) kinase-1.
Phosphorylation of liver glycogen synthase by cAMP-dependent protein kinase (A-kinase) results in the incorporation of approximately 0.7 to 1.0 mol of PO4/subunit. Analyses of the tryptic peptides by isoelectric focusing and peptide mapping reveal the presence of a single 32P-labeled peptide. This extent of phosphorylation does not result in a significant reduction of the synthase activity ratio. Phosphorylation of the liver synthase by cAMP-independent synthase (casein) kinase-1 results in the incorporation of 1.6 to 2.2 mol of PO4/subunit. Although at least 4 tryptic peptides have been found to be labeled with 32P, no significant reduction of the synthase activity ratio was observed. Under the same assay conditions, the muscle synthase is effectively inactivated by either kinase alone or in combination. Inactivation of liver synthase can be achieved after phosphorylation by A-kinase and followed by synthase (casein) kinase-1. However, the inactivation becomes less effective if the order of the addition of these two kinases is reversed. Under the latter assay condition, the phosphate incorporation is less than additive in the presence of both kinases. Prior phosphorylation of the synthase by A-kinase transforms the synthase to become a better substrate for synthase (casein) kinase-1 as evidenced by a 3- to 5-fold increase in the rate of phosphorylation. This increased rate of phosphorylation of the synthase by synthase (casein) kinase-1 results from the rapid phosphorylation of a site neighboring to that previously phosphorylated by A-kinase.
D000818:Animals; D047388:Casein Kinases; D000242:Cyclic AMP / Q000494:pharmacology*; D006006:Glycogen Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008970:Molecular Weight; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats
D000242:Cyclic AMP; D006006:Glycogen Synthase; D011494:Protein Kinases; D047388:Casein Kinases