The intracellular location of phosphoprotein phosphatase activity.

The rapid appearance of radioactivity in the phosphoprotein fraction of tissues after exposure to inorganic radiophosphate was first noted by Davidson et al. (1). This finding was subsequently confirmed in several laboratories for a variety of cell types (2-5). The physiological function of phosphoproteins is obscure, however, since no direct evidence is yet available for their role in cell metabolism. Phosphoproteins such as casein can be phosphorylated by an enzyme present in mitochondria with adenosine triphosphate as the phosphate donor (6-9). A specific enzyme, phosphoprotein phosphatase, is capable of hydrolyzing the ester linkage. The phosphatase was originally found in frog eggs by Harris (lo), and it has been subsequently demonstrated in various tissues (11-13). We have recently reported on the properties of a phosphoprotein phosphatase occurring in the cytoplasmic particles of mouse liver (14). Construction of a hypothesis for the function of phosphoproteins in metabolism would be considerably aided by, and must be in agreement with, knowledge of the intracellular sites of the enzymes concerned in their metabolism. The observations reported here concern the intracellular location of the particulate phosphatase, and the existence of a second phosphoprotein phosphatase in the soluble phase of the cell. In addition, a particulate endogenous inhibitor of the soluble enzyme has been demonstrated.