Dephosphorylation of 1D-myo-inositol 1,4-bisphosphate in rat liver

Dephosphorylation of 1D-myo-inositol 1,4-bisphosphate [Ins(1,4)P₂] in rat liver is catalysed by a cytosolic phosphatase that removes the 1-phosphate group. The K(m) for Ins(1,4)P₂ is approx. 17 μM. Li⁺ (100 mM) causes 50% inhibition of Ins(1,4)P₂ phosphatase activity when activity is measured at the very low substrate concentration of 10 nM, but on raising the substrate concentration to 100 μM there is a greater than 10-fold increase in sensitivity to Li⁺, suggesting that Li⁺ acts mainly, but not entirely, as an uncompetitive inhibitor of Ins(1,4)P₂ phosphatase. In addition, rat liver cytosol shows Li⁺-sensitive phosphatase activity against 1D-myo-inositol 1-,3- and 4-monophosphates. The Ins(1,4)P₂ 1-phosphatase and inositol monophosphatase activities all share an apparent M(r) of 47 x 10³, as determined by gel-filtration chromatography. However, the Ins(1,4)P₂ 1-phosphatase is more sensitive to inactivation by heat, and can be separated from inositol monophosphatase activity by anion-exchange chromatography. We conclude that rat liver cytosol contains an Ins(1,4)P₂ 1-phosphatase that is distinct from, but in many ways similar to, inositol monophosphatase.