REGULATORY SUBUNIT OF THE TYPE-I CAMP-DEPENDENT PROTEIN-KINASE AS AN INHIBITOR AND SUBSTRATE OF THE CGMP-DEPENDENT PROTEIN-KINASE

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 255  (3) , 1164-1169
Abstract
The regulatory subunit of the type I [bovine heart] c[cyclic]AMP-dependent protein kinase (RI) serves as a substrate for the phosphotransferase reaction catalyzed by [bovine lung] cGMP-dependent protein kinase (Km = 2.2 .mu.M). The reaction is stimulated by cGMP when RI.cntdot.cAMP is the substrate, but not when nucleotide-free RI is used. The cGMP-dependent protein kinase catalyzes the incorporation of 2 mol of phosphate/mol of RI dimer in the presence of cAMP and a self-phosphorylation reaction to the extent of 4 mol of phosphate/mol of enzyme dimer. In the absence of cAMP, RI is a competitive inhibitor of the phosphorylation of histone H2B (Ki = 0.25 .mu.M) and of the synthetic peptide substrate Leu-Arg-Arg-Ala-Ser-Leu-Gly (Ki = 0.15 .mu.M) by the cGMP-dependent enzyme. Nucleotide-free RI also inhibits the intramolecular self-phosphorylation of cGMP-dependent protein kinase. The inhibition of the phosphorylation reactions are reversed by cAMP. The catalytic subunit of cAMP-dependent protein kinase does not catalyze the phosphorylation of RI and does not significantly alter the ability of RI to serve as a substrate or an inhibitor of cGMP-dependent protein kinase. These observations are consistent with the concept that the cGMP- and cAMP-dependent protein kinases are closely related proteins whose functional domains may interact.