A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity,3 '-phosphoadenosine 5 '-phosphate phosphatase and inositol-polyphosphate 1-phosphatase

We report the molecular cloning in Rattus norvegicus of a novel mammalian e nzyme (RnPIP), which shows both 3'-phosphoadenosine 5'-phosphate (PAP) phos phatase and inositol-polyphosphate l-phosphatase activities. This enzyme is the first PAP phosphatase characterized at the molecular level in mammals, and it represents the first member of a novel family of dual specificity e nzymes. The phosphatase activity is strictly dependent on Mg2+, and it is i nhibited by Ca2+ and Li+ ions. Lithium chloride inhibits the hydrolysis of both PAP and inositol-1,4-bisphosphate at submillimolar concentration; ther efore, it is possible that the inhibition of the human homologue of RnPIP b y lithium ions is related to the pharmacological action of lithium. We prop ose that the PAP phosphatase activity of RnPIP is crucial for the function of enzymes sensitive to inhibition by PAP, such as sulfotransferase and RNA processing enzymes. Finally, an unexpected connection between PAP and inos itol-1,4-bisphosphate metabolism emerges from this work.