The identification and characterization of two phosphatidylinositol-4,5- bisphosphate 4-phosphatases

Alexander Ungewickell, Christopher Hugge, Marina Kisseleva, Shao Chun Chang, Jun Zou, Yucheng Feng, Edouard E. Galyov, Monita Wilson, Philip W. Majerus

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

Numerous inositol polyphosphate 5-phosphatases catalyze the degradation of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P). An alternative pathway to degrade PtdIns-4,5-P2 is the hydrolysis of PtdIns-4,5-P2 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-P2 4-phosphatase type I and type II, which catalyze the hydrolysis of PtdIns-4,5-P2 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.

Original languageEnglish (US)
Pages (from-to)18854-18859
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number52
DOIs
StatePublished - Dec 27 2005
Externally publishedYes

Keywords

  • Cell signaling
  • Lysosome
  • Phosphatidylinositol 5-phosphate

ASJC Scopus subject areas

  • General

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