Document Detail


Sequential actions of phospholipase D and phosphatidic acid phosphohydrolase 2b generate diglyceride in mammalian cells.
MedLine Citation:
PMID:  10564277     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phosphatidylcholine (PC) is a major source of lipid-derived second messenger molecules that function as both intracellular and extracellular signals. PC-specific phospholipase D (PLD) and phosphatidic acid phosphohydrolase (PAP) are two pivotal enzymes in this signaling system, and they act in series to generate the biologically active lipids phosphatidic acid (PA) and diglyceride. The identity of the PAP enzyme involved in PLD-mediated signal transduction is unclear. We provide the first evidence for a functional role of a type 2 PAP, PAP2b, in the metabolism of PLD-generated PA. Our data indicate that PAP2b localizes to regions of the cell in which PC hydrolysis by PLD is taking place. Using a newly developed PAP2b-specific antibody, we have characterized the expression, posttranslational modification, and localization of endogenous PAP2b. Glycosylation and localization of PAP2b appear to be cell type and tissue specific. Biochemical fractionation and immunoprecipitation analyses revealed that PAP2b and PLD2 activities are present in caveolin-1-enriched detergent-resistant membrane microdomains. We found that PLD2 and PAP2b act sequentially to generate diglyceride within this specialized membrane compartment. The unique lipid composition of these membranes may provide a selective environment for the regulation and actions of enzymes involved in signaling through PC hydrolysis.
Authors:
V A Sciorra; A J Morris
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular biology of the cell     Volume:  10     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-12-09     Completed Date:  1999-12-09     Revised Date:  2013-04-17    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3863-76     Citation Subset:  IM    
Affiliation:
Department of Pharmacological Sciences and Institute for Cell and Developmental Biology, State University of New York, Stony Brook, New York 11794-8651, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Caveolin 1
Caveolins*
Cell Line
Cell Membrane / metabolism
Detergents
Diglycerides / metabolism*
Fluorescent Antibody Technique
Gene Expression
Humans
Membrane Proteins / metabolism
Mice
Molecular Sequence Data
Peptide Fragments / immunology
Phosphatidate Phosphatase / genetics,  metabolism*
Phospholipase D / metabolism*
Phosphorylation
Protein Processing, Post-Translational / genetics
Signal Transduction
Tetradecanoylphorbol Acetate
Grant Support
ID/Acronym/Agency:
GM-54388/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/CAV1 protein, human; 0/Cav1 protein, mouse; 0/Caveolin 1; 0/Caveolins; 0/Detergents; 0/Diglycerides; 0/Membrane Proteins; 0/Peptide Fragments; 16561-29-8/Tetradecanoylphorbol Acetate; EC 3.1.3.4/Phosphatidate Phosphatase; EC 3.1.4.4/Phospholipase D
Comments/Corrections

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