The Identification and Characterization of Two Phosphatidylinositol-4,5-Bisphosphate 4-Phosphatases

Numerous inositol polyphosphate 5-phosphatases catalyze the degradation of phosphatidylinositol-4,5-bisphosphate ($PtdIns-4,5-P_2$) to phosphatidylinositol-4-phosphate (PtdIns-4-P). An alternative pathway to degrade$PtdIns-4,5-P_2$is the hydrolysis of$PtdIns-4,5-P_2$by a 4-phosphatase, leading to the production of PtdIns-5-P. Whereas the bacterial IpgD enzyme is known to catalyze this reaction, no such mammalian enzyme has been found. We have identified and characterized two previously undescribed human enzymes,$PtdIns-4,5-P_2$4-phosphatase type I and type II, which catalyze the hydrolysis of$PtdIns-4,5-P_2$to phosphatidylinositol-5-phosphate (PtdIns-5-P). Both enzymes are ubiquitously expressed and localize to late endosomal/lysosomal membranes in epithelial cells. Overexpression of either enzyme in HeLa cells increases EGF-receptor degradation upon EGF stimulation.