SUBUNIT STRUCTURE AND REGULATION OF PROTEIN PHOSPHATASE-1 IN RAT-LIVER NUCLEI

The activity of protein phosphatase-1 in rat liver nuclei (PP-1N) was decreased by up to 97% by associated inhibitory polypeptides, dependin g on the assay and extraction conditions. These inhibitors were rapidl y degraded by endogenous proteases, resulting in the accumulation of a ctive heat stable intermediates. Two major species of PP-1N could be d ifferentiated by fractionation of a nuclear extract. PP-1N(R111) conta ined, besides the delta-isoform of the catalytic subunit, an inhibitor y polypeptide of 111 kDa, PP-1N(R41) was found to be an inactive heter odimer between the delta-isoform of the catalytic subunit and NIPP-1, a nuclear inhibitor of PP-1, which in its undegraded form is heat labi le and migrates during SDS-polyacrylamide gel electrophoresis as a pol ypeptide of 41 kDa. Native hepatic NIPP-1 displayed a reduced affinity for the catalytic subunit after phosphorylation by protein kinase A i n vitro and after glucagon-induced phosphorylation in vivo.