| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 281, Issue 14, 9490-9497, April 7, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
12
From the
Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, and the Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115 and the ¶Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599
Presqualene diphosphate (PSDP) is a bioactive lipid that rapidly remodels to presqualene monophosphate (PSMP) upon cell activation (Levy, B. D., Petasis, N. A., and Serhan, C. N. (1997) Nature 389, 985–990). Here, we have identified and characterized a phosphatase that converts PSDP to PSMP. Unlike the related polyisoprenyl phosphate farnesyl diphosphate (FDP), PSDP was not a substrate for type 2 lipid phosphate phosphohydrolases. PSDP phosphatase activity was identified in activated human neutrophil (PMN) extracts and partially purified in the presence of Nonidet P-40 with gel filtration and anion exchange chromatography. Peptide sequencing of a candidate phosphatase was consistent with phosphatidic acid phosphatase domain containing 2 (PPAPDC2), an uncharacterized protein that contains a lipid phosphate phosphohydrolase consensus motif. Recombinant PPAPDC2 displayed diphosphate phosphatase activity with a substrate preference for PSDP > FDP > phosphatidic acid. PPAPDC2 activity was independent of Mg2+ and optimal at pH 7.0 to 8.0. Incubation of [14C]FDP with recombinant human squalene synthase led to [14C]PSDP and [14C]squalene formation, and in the presence of PPAPDC2, [14C]PSMP was generated from [14C]PSDP. PPAPDC2 mRNA was detected in human PMN, and is widely expressed in human tissues. Together, these findings indicate that PPAPDC2 in human PMN is the first lipid phosphate phosphohydrolase identified for PSDP. Regulation of this activity of the enzyme may have important roles for PMN activation in innate immunity.
Received for publication, December 5, 2005 , and in revised form, February 6, 2006.
* This work was supported in part by National Institutes of Health Grants HL68669 and P50-DE016191 (to B. D. L.) and post-doctoral fellowships from Pfizer and the Uehara Memorial Research Foundation (to K. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Supported by the Japanese Society for the Promotion of Science for Research Abroad.
2 To whom correspondence should be addressed. Tel.: 617-732-4353; Fax: 617-732-7421; E-mail: blevy{at}partners.org.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  N. M. Jackson and T. A. Kocarek Suppression of CYP2B Induction by Alendronate-Mediated Farnesyl Diphosphate Synthase Inhibition in Primary Cultured Rat Hepatocytes Drug Metab. Dispos., October 1, 2008; 36(10): 2030 - 2036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Haworth and B. D. Levy Endogenous lipid mediators in the resolution of airway inflammation Eur. Respir. J., November 1, 2007; 30(5): 980 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bonnans and B. D. Levy Lipid Mediators as Agonists for the Resolution of Acute Lung Inflammation and Injury Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 201 - 205. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
