Document Detail


Interleukin-2 causes an increase in saturated/monounsaturated phosphatidic acid derived from 1,2-diacylglycerol and 1-O-alkyl-2-acylglycerol.
MedLine Citation:
PMID:  10358029     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phosphatidic acid generation through activation of diacylglycerol kinase alpha has been implicated in interleukin-2-dependent T-lymphocyte proliferation. To investigate this lipid signaling in more detail, we characterized the molecular structures of the diradylglycerols and phosphatidic acids in the murine CTLL-2 T-cell line under both basal and stimulated conditions. In resting cells, 1,2-diacylglycerol and 1-O-alkyl-2-acylglycerol subtypes represented 44 and 55% of total diradylglycerol, respectively, and both showed a highly saturated profile containing primarily 16:0 and 18:1 fatty acids. 1-O-Alk-1'-enyl-2-acylglycerol represented 1-2% of total diradylglycerol. Interleukin-2 stimulation did not alter the molecular species profiles, however, it did selectively reduce total 1-O-alkyl-2-acylglycerol by over 50% at 15 min while only causing a 10% drop in 1,2-diacylglycerol. When radiolabeled CTLL-2 cells were challenged with interleukin-2, no change in the cellular content of phosphatidylcholine nor phosphatidylethanolamine was observed thereby ruling out phospholipase C activity as the source of diradylglycerol. In addition, interleukin-2 failed to stimulate de novo synthesis of diradylglycerol. Structural analysis revealed approximately equal amounts of 1,2-diacyl phosphatidic acid and 1-O-alkyl-2-acyl phosphatidic acid under resting conditions, both containing only saturated and monounsaturated fatty acids. After acute (2 and 15 min) interleukin-2 stimulation the total phosphatidic acid mass increased, almost entirely through the formation of 1-O-alkyl-2-acyl species. In vitro assays revealed that both 1,2-diacylglycerol and 1-O-alkyl-2-acylglycerol were substrates for 1,2-diacylglycerol kinase alpha, the major isoform in CTLL-2 cells, and that the lipid kinase activity was almost totally inhibited by R59949. In conclusion, this investigation shows that, in CTLL-2 cells, 1,2-diacylglycerol kinase alpha specifically phosphorylates a pre-existing pool of 1-O-alkyl-2-acylglycerol to form the intracellular messenger 1-O-alkyl-2-acyl phosphatidic acid.
Authors:
D R Jones; T R Pettitt; M A Sanjuán; I Mérida; M J Wakelam
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  274     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-07-06     Completed Date:  1999-07-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  16846-52     Citation Subset:  IM    
Affiliation:
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Cantoblanco, 28049, Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromatography, High Pressure Liquid
Diacylglycerol Kinase / metabolism
Diglycerides / biosynthesis,  metabolism*
Fatty Acids / analysis,  metabolism*
Fatty Acids, Unsaturated / analysis,  metabolism
Gas Chromatography-Mass Spectrometry
Interleukin-2 / pharmacology*
Isoenzymes / metabolism
Mice
Phosphatidic Acids / biosynthesis*,  chemistry
T-Lymphocytes / metabolism*
Chemical
Reg. No./Substance:
0/1,2-diacylglycerol; 0/Diglycerides; 0/Fatty Acids; 0/Fatty Acids, Unsaturated; 0/Interleukin-2; 0/Isoenzymes; 0/Phosphatidic Acids; 82231-61-6/diarachidonyl diglyceride; EC 2.7.1.107/Diacylglycerol Kinase

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