Home LiteratureArticle Details
PMID: 16365287 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 52 ·2005-12-27 ·Pages 18854-9

Ungewickell A, Hugge C, Kisseleva M, Chang SC, Zou J, Feng Y, Galyov EE, Wilson M, Majerus PW

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.

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,metabolism Phosphatidylinositols/chemistry Phosphoric Monoester Hydrolases/chemistry,metabolism RNA, Messenger/metabolism RNA, Small Interfering/metabolism Sequence Homology, Amino Acid Signal Transduction Time Factors Tissue Distribution Transfection
Chemicals
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
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ungewickell Alexander
Division of Hematology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hugge Christopher
Kisseleva Marina
Chang Shao-Chun
Zou Jun
Feng Yucheng
Galyov Edouard E
Wilson Monita
Majerus Philip W
References (28)
28 references, click to expand
  1. Inositol lipids are regulated during cell cycle progression in the nuclei of murine erythroleukaemia cells.
    Biochem J. 2001 Aug 1;357(Pt 3):905-10 PMID: 11463365
  2. PI(4,5)P(2) regulation of surface membrane traffic.
    Curr Opin Cell Biol. 2001 Aug;13(4):493-9 PMID: 11454457
  3. Phosphoinositide-specific inositol polyphosphate 5-phosphatase IV inhibits Akt/protein kinase B phosphorylation and leads to apoptotic cell death.
    J Biol Chem. 2002 Feb 22;277(8):6266-72 PMID: 11706019
  4. Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the S.flexneri effector IpgD reorganizes host cell morphology.
    EMBO J. 2002 Oct 1;21(19):5069-78 PMID: 12356723
  5. Phosphatidylinositol 5-phosphate biosynthesis is linked to PIKfyve and is involved in osmotic response pathway in mammalian cells.
    J Biol Chem. 2002 Dec 6;277(49):47276-84 PMID: 12270933
  6. PTEN and myotubularin phosphatases: from 3-phosphoinositide dephosphorylation to disease.
    Trends Cell Biol. 2002 Dec;12(12):579-85 PMID: 12495846
  7. Phosphatidylinositol-5-phosphate activation and conserved substrate specificity of the myotubularin phosphatidylinositol 3-phosphatases.
    Curr Biol. 2003 Mar 18;13(6):504-9 PMID: 12646134
  8. The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor.
    Cell. 2003 Jul 11;114(1):99-111 PMID: 12859901
  9. Allosteric activation of PTEN phosphatase by phosphatidylinositol 4,5-bisphosphate.
    J Biol Chem. 2003 Sep 5;278(36):33617-20 PMID: 12857747
  10. PI3P signaling regulates receptor sorting but not transport in the endosomal pathway.
    J Cell Biol. 2003 Sep 15;162(6):971-9 PMID: 12975344
  11. Production of phosphatidylinositol 5-phosphate by the phosphoinositide 3-phosphatase myotubularin in mammalian cells.
    J Biol Chem. 2004 Feb 20;279(8):7304-12 PMID: 14660569
  12. The biogenesis of multivesicular endosomes.
    Nat Rev Mol Cell Biol. 2004 Apr;5(4):317-23 PMID: 15071556
  13. Attenuated virulence and protective efficacy of a Burkholderia pseudomallei bsa type III secretion mutant in murine models of melioidosis.
    Microbiology. 2004 Aug;150(Pt 8):2669-76 PMID: 15289563
  14. The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian ESCRT-I and mediates receptor down-regulation.
    Mol Biol Cell. 2004 Sep;15(9):4337-46 PMID: 15240819
  15. Role for a novel signaling intermediate, phosphatidylinositol 5-phosphate, in insulin-regulated F-actin stress fiber breakdown and GLUT4 translocation.
    Endocrinology. 2004 Nov;145(11):4853-65 PMID: 15284192
  16. The discovery of a 3-phosphomonoesterase that hydrolyzes phosphatidylinositol 3-phosphate in NIH 3T3 cells.
    J Biol Chem. 1989 Nov 25;264(33):19911-5 PMID: 2555336
  17. AP-2-containing clathrin coats assemble on mature lysosomes.
    J Cell Biol. 1996 Dec;135(6 Pt 2):1801-14 PMID: 8991092
  18. A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate.
    Nature. 1997 Nov 13;390(6656):192-6 PMID: 9367159
  19. SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase.
    Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14057-9 PMID: 9826652
  20. Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body.
    Cell. 1998 Dec 11;95(6):847-58 PMID: 9865702
  21. The role of phosphatases in inositol signaling reactions.
    J Biol Chem. 1999 Apr 16;274(16):10669-72 PMID: 10196133
  22. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway.
    Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4240-5 PMID: 10200246
  23. Effects of lipid kinase expression and cellular stimuli on phosphatidylinositol 5-phosphate levels in mammalian cell lines.
    FEBS Lett. 2005 May 23;579(13):2868-72 PMID: 15876433
  24. Increased levels of inositol hexakisphosphate (InsP6) protect HEK293 cells from tumor necrosis factor (alpha)- and Fas-induced apoptosis.
    J Biol Chem. 2005 Aug 12;280(32):29263-8 PMID: 15967797
  25. An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway.
    J Cell Biol. 2005 Aug 15;170(4):607-18 PMID: 16103228
  26. Thrombin stimulation of platelets causes an increase in phosphatidylinositol 5-phosphate revealed by mass assay.
    FEBS Lett. 2000 Jun 9;475(1):57-60 PMID: 10854858
  27. Back in the water: the return of the inositol phosphates.
    Nat Rev Mol Cell Biol. 2001 May;2(5):327-38 PMID: 11331907
  28. Phosphoinositides, key molecules for regulation of actin cytoskeletal organization and membrane traffic from the plasma membrane.
    Biochim Biophys Acta. 2001 Oct 31;1533(3):190-206 PMID: 11731330
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0509740102
Published
2005-12-27
Epub
2005-00-19
Pages
18854-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1323219
Subset
IM
Grants
NHLBI NIH HHS · R01 HL016634 · United States
NIAID NIH HHS · U54 AI057160 · United States
NHLBI NIH HHS · HL 16634 · United States
NHLBI NIH HHS · HL 55272 · United States
External Links
PubMed source DOI: 10.1073/pnas.0509740102 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2