Lysophospholipid receptors in cell signaling

Torkhovskaya, T. I.; Ipatova, O. M.; Zakharova, T. S.; Kochetova, M. M.; Khalilov, E. M.

doi:10.1134/s0006297907020010

Cited by 33 publications

(25 citation statements)

References 67 publications

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“…An alternative mechanism through which exogenous PA activates ERK and mTORC1 is through its hydrolysis to LPA by phospholipases (i.e., phospholipase A) present in the culture medium, followed by subsequent binding of LPA to endothelial differentiation gene (EDG) receptors. Activation of EDG receptors would then lead to increased signaling through the MEK-ERK pathway (52). Phospholipase A is present in serum (35) and is also secreted by cells in culture (27,39).…”

Section: Discussionmentioning

confidence: 99%

Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway

Winter

Fox

Kester

et al. 2010

American Journal of Physiology-Cell Physiology

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The mammalian target of rapamycin (mTOR) assembles into two distinct multiprotein complexes known as mTORC1 and mTORC2. Of the two complexes, mTORC1 acts to integrate a variety of positive and negative signals to downstream targets that regulate cell growth. The lipid second messenger, phosphatidic acid (PA), represents one positive input to mTORC1, and it is thought to act by binding directly to mTOR, thereby enhancing the protein kinase activity of mTORC1. Support for this model includes findings that PA binds directly to mTOR and addition of PA to the medium of cells in culture results in activation of mTORC1. In contrast, the results of the present study do not support a model in which PA activates mTORC1 through direct interaction with the protein kinase but, instead, show that the lipid promotes mTORC1 signaling through activation of the ERK pathway. Moreover, rather than acting directly on mTORC1, the results suggest that exogenous PA must be metabolized to lysophosphatidic acid (LPA), which subsequently activates the LPA receptor endothelial differentiation gene (EDG-2). Finally, in contrast to previous studies, the results of the present study demonstrate that leucine does not act through phospholipase D and PA to activate mTORC1 and, instead, show that the two mediators act through parallel upstream signaling pathways to activate mTORC1. Overall, the results demonstrate that leucine and PA signal through parallel pathways to activate mTORC1 and that PA mediates its effect through the ERK pathway, rather than through direct binding to mTOR. leucine; phospholipase D; insulin; MEK; lysophosphatidic acid THE MAMMALIAN TARGET OF RAPAMYCIN (mTOR) is a serinethreonine protein kinase that functions as a nutrient sensor and acts to govern a wide range of cellular processes, including cell growth, proliferation, metabolism, autophagy, and survival (28, 34).

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Section: Discussionmentioning

confidence: 99%

Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway

Winter

Fox

Kester

et al. 2010

American Journal of Physiology-Cell Physiology

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“…It is known that some LPLs act in a wide range of animal cells as growth factors with hormone-like biological activities. They initiate and regulate cell proliferation including mitosis, cell differentiation and migration, and affect cell viability through anti-apoptosis properties (Birgbauer and Chun, 2006;Torkhovskaya et al, 2007). Considering their role among metazoans, one hypothesis is that they act as signaling molecules or metabolic intermediates during embryogenesis.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Among them, lysophospholipids (LPLs) represent only 0.5 to 6% of the whole PL content of cell membranes (Birgbauer and Chun, 2006;Torkhovskaya et al, 2007), their structural role being considered minor. However, they are recognized as second messenger molecules in cellular signal transduction processes (Torkhovskaya et al, 2007;D'Arrigo and Servi, 2010). These molecules exhibit a wide range of biological activities, and are among the most interesting lipids for pharmaceutical applications (Moolenaar, 2000;Birgbauer and Chun, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Lysophospholipids in the Mediterranean Sponge Oscarella tuberculata: Seasonal Variability and Putative Biological Role

Ivanišević¹,

Pérez²,

Ereskovsky³

et al. 2011

J Chem Ecol

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Lysophospholipids (LPLs) are recognized as important signaling molecules in metazoan cells. LPLs seem to be widely distributed among marine invertebrates, but their physiological role remains poorly known. Marine sponges produce original phospholipids and LPLs whose isolation and structural elucidation rarely have been reported. Two LPLs were isolated for the first time from the Mediterranean Homoscleromorph sponge Oscarella tuberculata: a bioactive lyso-PAF already identified in some other sponge species; and the new lysophosphatidylethanolamine C20:2 (LPE 1). The expression of LPL metabolites was investigated over time to determine their baseline variations and to relate them to the sponge reproduction pattern in order to better understand their putative role in the sponge life cycle. Expression levels of both compounds appeared to be highly correlated displaying significant seasonal fluctuations with maximal values in summer and minimal in winter. A significant higher LPL content was detected in reproductive sponges and especially in females, with a peak occurring during embryogenesis and larval development. The results suggest that LPLs could play a role of mediators in sponge embryogenesis and morphogenesis.

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“…Previous studies demonstrated that lyso-PC bind and activate G protein-coupled receptor (GPCR) [30]. To test the involvement of GPCR on lyso-PC signaling, peritoneal macrophages from both wild-type and TLR2 Ϫ/Ϫ mice were treated with the Gai inhibitor, pertussis toxin (100 ng/mL), for 30 min before treatment with lyso-PC.…”

Section: S Mansoni-induced Eosinophil Recruitment and Activation Occmentioning

confidence: 99%

Schistosomal‐Derived Lysophosphatidylcholine Are Involved in Eosinophil Activation and Recruitment through Toll‐Like Receptor–2–Dependent Mechanisms

es¹,

Almeida²,

Atella³

et al. 2010

J INFECT DIS

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Parasite‐derived lipids may play important roles in host‐pathogen interactions and escape mechanisms. Herein, we evaluated the role of schistosomal‐derived lipids in Toll‐like receptor (TLR)-2 and eosinophil activation in Schistosoma mansoni infection. Mice lacking TLR2 exhibited reduced liver eosinophilic granuloma, compared with that of wild‐type animals, following S. mansoni infection. Decreased eosinophil accumulation and eosinophil lipid body (lipid droplet) formation, at least partially due to reduced production of eotaxin, interleukin (IL)‐5, and IL‐13 in S. mansoni-infected TLR2-/- mice, compared with the corresponding production in wild‐type mice, was noted. Although no differences were observed in survival rates during the acute schistosomal infection (up to 50 days), increased survival of TLR2-/- mice, compared with survival of wild‐type mice, was observed during the chronic phase of infection. Schistosomal lipid extract– and schistosomal‐derived lysophosphatidylcholine (lyso‐PC)-stimulated macrophages in vitro induced TLR2‐dependent NF‐kB activation and cytokine production. Furthermore, in vivo schistosomal lyso‐PC administration induced eosinophil recruitment and cytokine production, in a mechanism largely dependent on TLR2. Taken together, our results suggest that schistosomal‐derived lyso‐PC may participate in cytokine production and eosinophil activation through a TLR2‐dependent pathway in S. mansoni infection. Moreover, our results suggest that TLR2‐dependent inflammatory reaction, cytokine production, and eosinophil recruitment and activation may contribute to the pathogenesis and lethality in the chronic phase of infection.

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Lysophospholipid receptors in cell signaling

Cited by 33 publications

References 67 publications

Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway

Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway

Lysophospholipids in the Mediterranean Sponge Oscarella tuberculata: Seasonal Variability and Putative Biological Role

Schistosomal‐Derived Lysophosphatidylcholine Are Involved in Eosinophil Activation and Recruitment through Toll‐Like Receptor–2–Dependent Mechanisms

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