Cyclic GMP-dependent protein kinase rapidly phosphorylates cardiac troponin inhibitory subunit (TN-I) at low concentrations, suggesting overlapping substrate specificity with cAMP-dependent kinase.
The study demonstrates overlapping substrate specificity for cAMP- and cGMP-dependent protein kinases on cardiac troponin, with both enzymes phosphorylating the same site on TN-I.
Cyclic AMP- and cGMP-dependent protein kinases catalyze the phosphorylation of cardiac troponin inhibitory subunit (TN-I). Unlike many substrates utilized by both kinases, TN-I is rapidly phosphorylated using relatively low concentrations of the cGMP-dependent protein kinase (0.01 to 0.1 micrometer). At low concentrations of cAMP- and cGMP-dependent protein kinases, approximately twice as much total phosphate is incorporated into TN-I using the cAMP-dependent enzyme. At higher enzyme concentrations, 1 mol of phosphate/mol of TN-I is found using either enzyme. Maximal levels of cAMP- and CGMP-dependent protein kinases do not catalyze additive phosphorylation, suggesting that the two enzymes catalyze the phosphorylation of the same site on TN-I. The results support the concept of overlapping substrate specificity for cAMP- and cGMP-dependent protein kinases, but suggest that cardiac troponin contains additional specificity determinants for the cGMP-dependent protein kinase not found in several other protein substrates.
Lincoln et al. (Sun,) reported a other. cGMP-dependent protein kinase vs. cAMP-dependent protein kinase was evaluated on Phosphorylation of cardiac troponin inhibitory subunit (TN-I). Cyclic GMP-dependent protein kinase rapidly phosphorylates cardiac troponin inhibitory subunit (TN-I) at low concentrations, suggesting overlapping substrate specificity with cAMP-dependent kinase.