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, depending on the assay and extraction conditions. These inhibitors were rapidly degraded by endogenous proteases, resulting in the accumulation of active heat stable intermediates. Two major species of PP-1N could be differentiated by fractionation of a nuclear extract. PP-1N(R111) contained, besides the delta-isoform of the catalytic subunit, an inhibitory polypeptide of 111 kDa, PP-1N(R41) was found to be an inactive heterodimer between the delta-isoform of the catalytic subunit and NIPP-1, a nuclear inhibitor of PP-1, which in its undegraded form is heat labile and migrates during SDS-polyacrylamide gel electrophoresis as a polypeptide of 41 kDa. Native hepatic NIPP-1 displayed a reduced affinity for the catalytic subunit after phosphorylation by protein kinase A in vitro and after glucagon-induced phosphorylation in vivo.