Human sphingosine-1-phosphate lyase: cDNA cloning, functional expression studies and mapping to chromosome 10q2211DNA sequence was deposited in the EMBL database (AJ011304).

Veldhoven, Paul P. Van; Gijsbers, Sofie; Mannaerts, Guy P.; Vermeesch, Joris Robert; Brys, Vanessa

doi:10.1016/s1388-1981(00)00079-2

Cited by 102 publications

(101 citation statements)

References 17 publications

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“…44 The first SPL gene to be identified was DPL1 (dihydrosphingosine-1-phosphate lyase), 45 which facilitated the identification of functional SPL homologs within the genomes of Caenorhabditis elegans, Dictyostelium discoideum, Leishmania major, Drosophila melanogaster, Mus musculus, and Homo sapiens. [46][47][48][49][50][51] Altered SPL expression in a variety of cell lines and mutant model systems has yielded pronounced effects and severe phenotypes. For example, S. cerevisiae dpl1 null mutants are Figure 1.…”

Section: S1p Lyasementioning

confidence: 99%

Sphingosine-1-Phosphate Metabolism and Intestinal Tumorigenesis: Lipid Signaling Strikes Again

Oskouian¹,

Saba²

2007

Cell Cycle

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Section: S1p Lyasementioning

confidence: 99%

Sphingosine-1-Phosphate Metabolism and Intestinal Tumorigenesis: Lipid Signaling Strikes Again

Oskouian¹,

Saba²

2007

Cell Cycle

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“…37 On the basis of their sequence similarity to the yeast lyase gene, cDNAs encoding murine and human S1P lyases were subsequently cloned. 38,39 Human S1P lyase is a 568 amino acid protein and is abundant in the liver. 39 Site-directed mutagenesis revealed the importance of cysteine residues 218 and 317 of the human enzyme for the cleavage reaction.…”

Section: S1p Metabolismmentioning

confidence: 99%

“…38,39 Human S1P lyase is a 568 amino acid protein and is abundant in the liver. 39 Site-directed mutagenesis revealed the importance of cysteine residues 218 and 317 of the human enzyme for the cleavage reaction. 39 S1P lyase, like S1P phosphatase, appears to be localized to the endoplasmic reticulum of cells.…”

Section: S1p Metabolismmentioning

confidence: 99%

Sphingosine 1-phosphate as a therapeutic agent

2002

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The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P), formed by activation of sphingosine kinase in response to diverse stimuli, is an important lipid mediator that has novel dual actions -both inside and outside of cells. S1P is the ligand for a family of five G protein-coupled receptors. Activation of these GPCRs by S1P or dihydro-S1P regulates diverse processes, including cell migration, angiogenesis, vascular maturation, heart development, and neurite retraction. There is also abundant evidence that S1P can function as a second messenger important for regulation of calcium homeostasis, cell growth, and suppression of apoptosis. In many cases, the intracellular level of S1P and ceramide, another important sphingolipid metabolite associated with cell death and cell growth arrest, coordinately determine cell fate. Changes in S1P and ceramide have been implicated in a number of pathological conditions in which apoptosis plays an important role. Importantly, radiation-induced oocyte loss in adult female mice, the event that drives premature ovarian failure and infertility in female cancer patients, was completely prevented by in vivo therapy with S1P. Understanding the biosynthesis, metabolism and functions of S1P can uncover new targets for the pharmaceutical and therapeutic applications of S1P.

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“…However, it has become clear that SPL expression is influenced by a variety of factors. For example, although SPL expression has been found in most mammalian tissues with the exception of blood platelets, the degree of expression demonstrated in mouse and human tissues is quite variable, with the highest levels in liver, kidney, and intestine and lesser amounts in muscle and brain (20,21). SPL expression in mouse embryonal carcinoma cells is upregulated during differentiation (22).…”

mentioning

confidence: 99%

Regulation of Sphingosine-1-phosphate Lyase Gene Expression by Members of the GATA Family of Transcription Factors

Oskouian¹,

Mendel

Shocron³

et al. 2005

Journal of Biological Chemistry

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Sphingosine-1-phosphate is a bioactive sphingolipid that regulates proliferation, differentiation, migration, and apoptosis. Sphingosine-1-phosphate is irreversibly degraded by the highly conserved enzyme sphingosine-1-phosphate lyase. Recent studies have suggested that sphingosine-1-phosphate lyase expression affects animal development and cell fate decisions. Despite its crucial role, mechanisms affecting expression of sphingosine-1-phosphate lyase remain poorly understood. In this study, regulation of sphingosine-1-phosphate lyase gene expression was investigated in Caenorhabditis elegans, where lyase expression is spatially restricted to cells of the developing and adult gut and is essential for normal development. Deletion analysis and generation of transgenic worms combined with fluorescence microscopy identified a 350-nucleotide sequence upstream of the ATG start site necessary for maximal lyase expression in adult worms. Site-specific mutagenesis of a GATA transcription factor-binding motif in the promoter led to loss of reporter expression. Knockdown of the gut-specific GATA transcription factor ELT-2 by RNA interference similarly led to loss of reporter expression. ELT-2 interacted with the GATA factorbinding motif in vitro and was also capable of driving expression of a Caenorhabditis elegans lyase promoter-␤-galactosidase reporter in a heterologous yeast system. These studies demonstrate that ELT-2 regulates sphingosine-1-phosphate lyase expression in vivo. Additionally, we demonstrate that the human sphingosine-1-phosphate lyase gene is regulated by a GATA transcription factor. Overexpression of GATA-4 led to both an increase in activity of a reporter gene as well as an increase in endogenous sphingosine-1-phosphate lyase protein.Sphingosine 1-phosphate (S1P) 1 is a sphingolipid signaling molecule that regulates cell proliferation, migration, and apoptosis and has been shown to play a role in mediating complex physiological processes, including vascular maturation, immune cell responses, and lymphocyte trafficking (1-7). S1P mediates many of its effects through activation of a subgroup of the Edg family of G protein-coupled receptors (8). Other effects, especially those related to cell survival, appear to be mediated through both receptor-dependent and receptor-independent mechanisms (9). Intracellular S1P levels are determined by the balance between its synthesis by phosphorylation of sphingosine, catalyzed by sphingosine kinase, and its recycling back to sphingosine catalyzed primarily by S1P phosphatase or its irreversible degradation to ethanolamine phosphate and hexadecenal, catalyzed by sphingosine-1-phosphate lyase (SPL) (10). Altered expression of each of the three major enzymes controlling S1P metabolism has been shown to affect mammalian cell fate decisions and survival (11-16). Understanding the physiological mechanisms by which the expression and activity of these enzymes are regulated may be useful in further elucidating the role of S1P in physiology and disease and in providing novel a...

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Human sphingosine-1-phosphate lyase: cDNA cloning, functional expression studies and mapping to chromosome 10q2211DNA sequence was deposited in the EMBL database (AJ011304).

Cited by 102 publications

References 17 publications

Sphingosine-1-Phosphate Metabolism and Intestinal Tumorigenesis: Lipid Signaling Strikes Again

Sphingosine-1-Phosphate Metabolism and Intestinal Tumorigenesis: Lipid Signaling Strikes Again

Sphingosine 1-phosphate as a therapeutic agent

Regulation of Sphingosine-1-phosphate Lyase Gene Expression by Members of the GATA Family of Transcription Factors

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