Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases

Amanda M. Gellett; Yugesh Kharel; Manjula Sunkara; Andrew J. Morris; Kevin R. Lynch

doi:10.1016/j.bbrc.2012.05.077

Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases

Amanda M. Gellett, Yugesh Kharel, Manjula Sunkara, Andrew J. Morris, Kevin R. Lynch

Internal Medicine

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Lysophosphatidic acid (LPA) designates a family of bioactive phosphoglycerides that differ in the length and degree of saturation of their radyl chain. Additional diversity is provided by the linkage of the radyl chain to glycerol: acyl, alkyl, or alk-1-enyl. Acyl-LPAs are the predominate species in tissues and biological fluids. Alkyl-LPAs exhibit distinct pharmacodynamics at LPA receptors, potently drive platelet aggregation, and contribute to ovarian cancer aggressiveness. Multiple biosynthetic pathways exist for alkyl-LPA production. Herein we report that diacylglycerol kinases (DGKs) contribute to cell-associated alkyl-LPA production involving phosphorylation of 1-alkyl-2-acetyl glycerol and document the biosynthesis of alkyl-LPA by DGKs in SKOV-3 ovarian cancer cells, specifically identifying the contribution of DGKα. Concurrently, we discovered that treating SKOV-3 ovarian cancer cell with a sphingosine analog stimulates conversion of exogenous 1-alkyl-2-acetyl glycerol to alkyl-LPA, indicating that DGKα contributes significantly to the production of alkyl-LPA in SKOV-3 cells and identifying cross-talk between the sphingolipid and glycerol lipid pathways.

Original language	English
Pages (from-to)	758-763
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	422
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2012.05.077
State	Published - Jun 15 2012

Bibliographical note

Funding Information:
The authors thank Kaoru Goto, M.D., Ph.D. for DGKα, DGKβ, and DGKγ cDNA; Fumio Sakane, Ph.D. for DGKδ1 and DGKδ2 cDNA and anti-DGKα, anti-DGKβ, anti-DGKγ, antibodies; and Matthew Topham, M.D. for DGKζ and DGKι cDNA. This work was supported by the NIH (R01 GM067958 K.R.L, T32 GM007055 A.M.G and R01 GM50388 and P20 RR021954 A.J.M).

Keywords

Alkyl lysophosphatidic acid
Alkylglycerol phosphate
Diacylglycerol kinase

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2012.05.077

Cite this

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title = "Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases",

abstract = "Lysophosphatidic acid (LPA) designates a family of bioactive phosphoglycerides that differ in the length and degree of saturation of their radyl chain. Additional diversity is provided by the linkage of the radyl chain to glycerol: acyl, alkyl, or alk-1-enyl. Acyl-LPAs are the predominate species in tissues and biological fluids. Alkyl-LPAs exhibit distinct pharmacodynamics at LPA receptors, potently drive platelet aggregation, and contribute to ovarian cancer aggressiveness. Multiple biosynthetic pathways exist for alkyl-LPA production. Herein we report that diacylglycerol kinases (DGKs) contribute to cell-associated alkyl-LPA production involving phosphorylation of 1-alkyl-2-acetyl glycerol and document the biosynthesis of alkyl-LPA by DGKs in SKOV-3 ovarian cancer cells, specifically identifying the contribution of DGKα. Concurrently, we discovered that treating SKOV-3 ovarian cancer cell with a sphingosine analog stimulates conversion of exogenous 1-alkyl-2-acetyl glycerol to alkyl-LPA, indicating that DGKα contributes significantly to the production of alkyl-LPA in SKOV-3 cells and identifying cross-talk between the sphingolipid and glycerol lipid pathways.",

keywords = "Alkyl lysophosphatidic acid, Alkylglycerol phosphate, Diacylglycerol kinase",

author = "Gellett, {Amanda M.} and Yugesh Kharel and Manjula Sunkara and Morris, {Andrew J.} and Lynch, {Kevin R.}",

note = "Funding Information: The authors thank Kaoru Goto, M.D., Ph.D. for DGKα, DGKβ, and DGKγ cDNA; Fumio Sakane, Ph.D. for DGKδ1 and DGKδ2 cDNA and anti-DGKα, anti-DGKβ, anti-DGKγ, antibodies; and Matthew Topham, M.D. for DGKζ and DGKι cDNA. This work was supported by the NIH (R01 GM067958 K.R.L, T32 GM007055 A.M.G and R01 GM50388 and P20 RR021954 A.J.M).",

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language = "English",

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AU - Gellett, Amanda M.

AU - Kharel, Yugesh

AU - Sunkara, Manjula

AU - Morris, Andrew J.

AU - Lynch, Kevin R.

N1 - Funding Information: The authors thank Kaoru Goto, M.D., Ph.D. for DGKα, DGKβ, and DGKγ cDNA; Fumio Sakane, Ph.D. for DGKδ1 and DGKδ2 cDNA and anti-DGKα, anti-DGKβ, anti-DGKγ, antibodies; and Matthew Topham, M.D. for DGKζ and DGKι cDNA. This work was supported by the NIH (R01 GM067958 K.R.L, T32 GM007055 A.M.G and R01 GM50388 and P20 RR021954 A.J.M).

PY - 2012/6/15

Y1 - 2012/6/15

N2 - Lysophosphatidic acid (LPA) designates a family of bioactive phosphoglycerides that differ in the length and degree of saturation of their radyl chain. Additional diversity is provided by the linkage of the radyl chain to glycerol: acyl, alkyl, or alk-1-enyl. Acyl-LPAs are the predominate species in tissues and biological fluids. Alkyl-LPAs exhibit distinct pharmacodynamics at LPA receptors, potently drive platelet aggregation, and contribute to ovarian cancer aggressiveness. Multiple biosynthetic pathways exist for alkyl-LPA production. Herein we report that diacylglycerol kinases (DGKs) contribute to cell-associated alkyl-LPA production involving phosphorylation of 1-alkyl-2-acetyl glycerol and document the biosynthesis of alkyl-LPA by DGKs in SKOV-3 ovarian cancer cells, specifically identifying the contribution of DGKα. Concurrently, we discovered that treating SKOV-3 ovarian cancer cell with a sphingosine analog stimulates conversion of exogenous 1-alkyl-2-acetyl glycerol to alkyl-LPA, indicating that DGKα contributes significantly to the production of alkyl-LPA in SKOV-3 cells and identifying cross-talk between the sphingolipid and glycerol lipid pathways.

AB - Lysophosphatidic acid (LPA) designates a family of bioactive phosphoglycerides that differ in the length and degree of saturation of their radyl chain. Additional diversity is provided by the linkage of the radyl chain to glycerol: acyl, alkyl, or alk-1-enyl. Acyl-LPAs are the predominate species in tissues and biological fluids. Alkyl-LPAs exhibit distinct pharmacodynamics at LPA receptors, potently drive platelet aggregation, and contribute to ovarian cancer aggressiveness. Multiple biosynthetic pathways exist for alkyl-LPA production. Herein we report that diacylglycerol kinases (DGKs) contribute to cell-associated alkyl-LPA production involving phosphorylation of 1-alkyl-2-acetyl glycerol and document the biosynthesis of alkyl-LPA by DGKs in SKOV-3 ovarian cancer cells, specifically identifying the contribution of DGKα. Concurrently, we discovered that treating SKOV-3 ovarian cancer cell with a sphingosine analog stimulates conversion of exogenous 1-alkyl-2-acetyl glycerol to alkyl-LPA, indicating that DGKα contributes significantly to the production of alkyl-LPA in SKOV-3 cells and identifying cross-talk between the sphingolipid and glycerol lipid pathways.

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Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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