Protein kinase C-dependent inhibition of the lysosomal degradation of endocytosed proteins in rat hepatocytes.

Abstract We studied the role of protein kinase C (PKC) in the lysosomal processing of endocytosed proteins in isolated rat hepatocytes. We used [ 14 C]sucrose-labeled horseradish peroxidase ([ 14 C]S-HRP) to simultaneously evaluate endocytosis and lysosomal proteolysis. The PKC activator phorbol 12-myristate 13-acetate (PMA) inhibited the lysosomal degradation of [ 14 C]S-HRP (1 μM PMA: 40% inhibition, P 14 C]S-HRP-loaded isolated lysosomes, suggesting that intracellular intermediates are required. PMA induced phosphorylation and hepatocyte membrane-to-lysosome redistribution of the myristoylated alanine-rich C kinase substrate (MARCKS) protein, raising the possibility that MARCKS mediates the PKC-induced inhibition of lysosomal proteolysis.