The Identification and Characterization of Two phosphatidylinositol-4,5-bisphosphate 4-phosphatases

Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18854-9. doi: 10.1073/pnas.0509740102. Epub 2005 Dec 19.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Burkholderia pseudomallei / metabolism
  • COS Cells
  • Catalysis
  • Cell Line
  • Chlorocebus aethiops
  • Cloning, Molecular
  • DNA, Complementary / metabolism
  • Endosomes / metabolism
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / metabolism
  • Fluorescent Dyes / pharmacology
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Hydrolysis
  • Inositol Polyphosphate 5-Phosphatases
  • Lysosomes / metabolism
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Phosphatidylinositol Phosphates / chemistry*
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphatidylinositols / chemistry
  • Phosphoric Monoester Hydrolases / chemistry*
  • Phosphoric Monoester Hydrolases / metabolism
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Time Factors
  • Tissue Distribution
  • Transfection

Substances

  • DNA, Complementary
  • Fluorescent Dyes
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • RNA, Messenger
  • RNA, Small Interfering
  • phosphatidylinositol 4-phosphate
  • Green Fluorescent Proteins
  • Epidermal Growth Factor
  • ErbB Receptors
  • Phosphoric Monoester Hydrolases
  • phosphoinositide 5-phosphatase
  • Inositol Polyphosphate 5-Phosphatases