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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-12, Vol.102 (52), p.18854-18859
• Main Authors: Ungewickell, Alexander, Christopher Hugge, Marina Kisseleva, Shao-Chun Chang, Zou, Jun, Feng, Yucheng, Galyov, Edouard E., Monita Wilson, Majerus, Philip W.
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Animals; Antibodies; Biochemistry; Biological Sciences; Blotting, Northern; Burkholderia pseudomallei - metabolism; Catalysis; Cell Line; Cercopithecus aethiops; Cloning, Molecular; COS Cells; DNA, Complementary - metabolism; Endosomes - metabolism; Enzymes; Epidermal Growth Factor - metabolism; Epithelial cells; Fluorescent Dyes - pharmacology; Green Fluorescent Proteins - metabolism; HEK293 cells; HeLa Cells; Humans; Hydrolysis; Inositol Polyphosphate 5-Phosphatases; Inositols; Lipids; Lysosomes - metabolism; Microscopy, Fluorescence; Molecular Sequence Data; Phosphatases; Phosphates; Phosphatidylinositol Phosphates - chemistry; Phosphatidylinositol Phosphates - metabolism; Phosphatidylinositols; Phosphatidylinositols - chemistry; Phosphoric Monoester Hydrolases - chemistry; Phosphoric Monoester Hydrolases - metabolism; Polyphosphates; Receptor, Epidermal Growth Factor - metabolism; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; Sequence Homology, Amino Acid; Signal Transduction; Time Factors; Tissue Distribution; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0509740102

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.