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 enzyme (RnPIP), which shows both 3'-phosphoadenosine 5'-phosphate (PAP) phosphatase and inositol-polyphosphate 1-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 enzymes. The phosphatase activity is strictly dependent on Mg2+, and it is inhibited by Ca2+ and Li+ ions. Lithium chloride inhibits the hydrolysis of both PAP and inositol-1,4-bisphosphate at submillimolar concentration; therefore, it is possible that the inhibition of the human homologue of RnPIP by lithium ions is related to the pharmacological action of lithium. We propose 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 inositol-1,4-bisphosphate metabolism emerges from this work.
López-Coronado
J M
JM
Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia-Consejo Superior de Investigaciones Científicas, Camino de Vera, E-46022, Valencia, Spain.
Bellés
J M
JM
Lesage
F
F
Serrano
R
R
Rodríguez
P L
PL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D006801:Humans; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity
D009097:Multienzyme Complexes; D010724:Phosphoadenosine Phosphosulfate; D008094:Lithium; C119648:Bpnt1 protein, rat; D010744:Phosphoric Monoester Hydrolases; C053087:inositol-1,4-bisphosphate 1-phosphatase; C027342:3'-phosphoadenosine-5'-phosphosulfate phosphohydrolase