Lysophospholipid signaling: Beyond the EDGs

Valentine, William J.; Fujiwara, Yuko; Tsukahara, Ryoko; Tigyi, Gábor

doi:10.1016/j.bbagen.2007.08.008

Cited by 23 publications

(15 citation statements)

References 53 publications

(81 reference statements)

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“…Studies now show that B103 cells express LPA4 and RH7777 cells express both LPA5 and PPARγ [29]. While these cells express only selective LPA receptors, they still maintain the genes for others.…”

Section: The Lpa1 Receptor As a Negative Regulator Of Ovarian Tumor Pmentioning

confidence: 97%

Sharpening the edges of understanding the structure/function of the LPA1 receptor: Expression in cancer and mechanisms of regulation☆

Murph

2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Since the molecular cloning of the vzg-1/Edg-2/LPA1 gene, studies have attempted to characterize LPA1 receptor functionality into a single categorical role, different from the other Edg-family LPA receptors. The desire to categorize LPA1 function has highlighted its complexity and demonstrated that the LPA1 receptor does not have one absolute function throughout every system. The central nervous system is highly enriched in the LPA1 receptor, suggesting an integral role in neuronal processes. Metastatic and invasive breast cancer also appears to have LPA-mediated LPA1 receptor functions that enhance phenotypes associated with tumorigenesis. LPA1 possesses a number of motifs conserved among G protein-coupled receptors (GPCRs): a DRY-like motif, a PDZ domain, Ser/Thr predicted sites of phosphorylation, a dileucine motif, double cysteines in the tail and conserved residues that stabilize structure and determine ligand binding. The third intracellular loop of the LPA1 receptor may be the crux of receptor signaling and attenuation with phosphorylation of Thr-236 potentially a key determinant of basal LPA1 signaling. Mutagenesis data supports the notion that Thr-236 regulates this process since mutating Thr-236 to Ala-236 increased basal and LPAmediated serum response factor (SRF) signaling activity and Lys-236 further increased this basal signaling. Here we describe progress on defining the major functions of the LPA1 receptor, discuss a context dependent dualistic role as both a negative regulator in cancer and a proto-oncogene, outline its structural components at the molecular amino-acid level and present mutagenesis data on the third intracellular loop of the receptor.

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Section: The Lpa1 Receptor As a Negative Regulator Of Ovarian Tumor Pmentioning

confidence: 97%

Sharpening the edges of understanding the structure/function of the LPA1 receptor: Expression in cancer and mechanisms of regulation☆

Murph

2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…number 3.1.4.39 (www.expasy.org). Because the main catalytic activity of ATX is the production of lysophosphatidic acid, it became clear that most, if not all, previously described roles were mediated by this phospholipid through its interaction with a family of seven transmembrane domain, G-coupled receptors (see for reviews [19][20][21].…”

Section: Enzyme Purificationmentioning

confidence: 99%

Autotaxin

Boutin

Ferry

2009

Cell. Mol. Life Sci.

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Autotaxin is a protein of approximately 900 amino acids discovered in the early 1990s. Over the past 15 years, a strong association between cancer cells and autotaxin production has been observed. Recent publications indicate that autotaxin and the capacity of cancer to metastasise are intimately linked. The discovery of new molecular targets in pharmacology is a mixture of pure luck, hard work and industrial strategy. Despite a crucial and desperate need for new therapeutic tools, many targets are approached in oncology, but only a few are validated and end up at the patient bed. Outside the busy domain of kinases, few targets have been discovered that can be useful in treating cancer, particularly metastatic processes. The fortuitous relationship between autotaxin and lysophosphatidic acid renders the results of observations made in the diabetes/obesity context considerably important. The literature provides observations that may aid in redesigning experiments to validate autotaxin as a potential oncology target.

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“…GPCRs of the endothelial differentiation gene family were the first to be recognized as LPA receptors, and they are designated LPA1 (Edg-2), LPA2 (Edg-4) and LPA3 (Edg-7). In addition to these classical LPA receptors three GPCRs of the purinergic family, GPR23/LPA4, GPR92/LPA5 and GPR87, have been recently identified to also mediate signaling via LPA [12–15]. Out of the above, LPA 1 and LPA3 have been described to be expressed by differentiating oligodendrocytes [16–20].…”

Section: Introductionmentioning

confidence: 99%

Lysophosphatidic Acid can Support the Formation of Membranous Structures and an Increase in MBP mRNA Levels in Differentiating Oligodendrocytes

et al. 2008

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During development, differentiating oligodendrocytes progress in distinct maturation steps from premyelinating to myelinating cells. Such maturing oligodendrocytes express both receptors mediating signaling via extracellular lysophosphatidic acid (LPA) and the major enzyme generating extracellular LPA, namely phosphodiesterase-Iα/autotaxin (PD-Iα/ATX). However, the biological role of extracellular LPA during the maturation of differentiating oligodendrocytes is currently unclear. Here, we demonstrate that application of exogenous LPA induced an increase in the area occupied by the oligodendrocytes' process network, but only when PD-Iα/ATX expression was down-regulated. This increase in network area was caused primarily by the formation of membranous structures. In addition, LPA increased the number of cells positive for myelin basic protein (MBP). This effect was associated by an increase in the mRNA levels coding for MBP but not myelin oligodendrocyte glycoprotein (MOG). Taken together, these data suggest that LPA may play a crucial role in regulating the later stages of oligodendrocyte maturation.

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Lysophospholipid signaling: Beyond the EDGs

Cited by 23 publications

References 53 publications

Sharpening the edges of understanding the structure/function of the LPA1 receptor: Expression in cancer and mechanisms of regulation☆

Sharpening the edges of understanding the structure/function of the LPA1 receptor: Expression in cancer and mechanisms of regulation☆

Autotaxin

Lysophosphatidic Acid can Support the Formation of Membranous Structures and an Increase in MBP mRNA Levels in Differentiating Oligodendrocytes

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