Integral membrane lipid phosphatases/phosphotransferases: common structure and diverse functions

Sigal, Yury J.; McDermott, Mark I.; Morris, Andrew J.

doi:10.1042/bj20041771

Cited by 182 publications

(235 citation statements)

References 100 publications

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“…Alternatively, the ecto-activity could enable mono-oleoylglycerol formed from oleoyl-LPA to enter the cell and thereby regulate cell signaling after re-phosphorylation (11,12). For example, intracellular LPA could signal through internal LPA receptors (47) or the PPAR␥ receptors (48,49) and thereby affect migration.…”

Section: Lpp1 Activity Regulates the Stimulation Of Fibroblast Migratmentioning

confidence: 99%

“…The present work focuses on the effects of the integral membrane protein, lipid phosphate phosphatase-1 (LPP1), which dephosphorylates LPA and other lipid phosphates, and the mechanisms whereby this enzyme modifies fibroblast migration. LPP1 acts partly in the plasma membrane as an ecto-enzyme (11,12). It was originally proposed that this ecto activity explained how LPP1 overexpression attenuated the effects of exogenous LPA in activating cell division, ERK, phospholipase D, and Ca 2ϩ transients (13,14).…”

mentioning

confidence: 99%

“…PA production in neutrophils stimulates NADPH oxidase. PA also stimulates protein kinase C-, phosphatidylinositol 4-kinase, and phospholipase C-␥ and increases Ras-GTP concentrations (11,12). It also increases sphingosine kinase-1 activity (26) and inhibits protein phosphatase-1 (27).…”

mentioning

confidence: 99%

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Lipid Phosphate Phosphatase-1 Regulates Lysophosphatidate-induced Fibroblast Migration by Controlling Phospholipase D2-dependent Phosphatidate Generation

Pilquil

Dewald

Cherney

et al. 2006

Journal of Biological Chemistry

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Section: Lpp1 Activity Regulates the Stimulation Of Fibroblast Migratmentioning

confidence: 99%

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confidence: 99%

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Lipid Phosphate Phosphatase-1 Regulates Lysophosphatidate-induced Fibroblast Migration by Controlling Phospholipase D2-dependent Phosphatidate Generation

Pilquil

Dewald

Cherney

et al. 2006

Journal of Biological Chemistry

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“…In mammals, two homologous genes, Sgpp1 and Sgpp2, encode the specific S1P phosphastases (8, 9) that belong to the superfamily of lipid phosphatases (6,10,11). Unlike the other lipid phosphatases in the family, which have broad substrate specificity, the SPPases are unique in that they are highly specific for sphingoid base phosphates.…”

mentioning

confidence: 99%

Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet β-Cell Endoplasmic Reticulum Stress and Proliferation

Taguchi¹,

Allende²,

Mizukami

et al. 2016

Journal of Biological Chemistry

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Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that regulates basic cell functions through metabolic and signaling pathways. Intracellular metabolism of S1P is controlled, in part, by two homologous S1P phosphatases (SPPases), 1 and 2, which are encoded by the Sgpp1 and Sgpp2 genes, respectively. SPPase activity is needed for efficient recycling of sphingosine into the sphingolipid synthesis pathway. SPPase 1 is important for skin homeostasis, but little is known about the functional role of SPPase 2. To identify the functions of SPPase 2 in vivo, we studied mice with the Sgpp2 gene deleted. In contrast to Sgpp1 ؊/؊ mice, Sgpp2 ؊/؊ mice had normal skin and were viable into adulthood. Unexpectedly, WT mice expressed Sgpp2 mRNA at high levels in pancreatic islets when compared with other tissues. Sgpp2 ؊/؊ mice had normal pancreatic islet size; however, they exhibited defective adaptive ␤-cell proliferation that was demonstrated after treatment with either a high-fat diet or the ␤-cell-specific toxin, streptozotocin. Importantly, ␤-cells from untreated Sgpp2 ؊/؊ mice showed significantly increased expression of proteins characteristic of the endoplasmic reticulum stress response compared with ␤-cells from WT mice, indicating a basal islet defect. Our results show that Sgpp2 deletion causes ␤-cell endoplasmic reticulum stress, which is a known cause of ␤-cell dysfunction, and reveal a juncture in the sphingolipid recycling pathway that could impact the development of diabetes.Sphingosine 1-phosphate (S1P) 3 is a potent bioactive lipid produced from the degradation of plasma membrane sphingolipids (1-3). As a signaling molecule, S1P exerts effects in a variety of biological processes through interactions with both extracellular receptors and intracellular targets. As an intracellular metabolic intermediate, S1P is readily metabolized to other bioactive sphingolipids, such as ceramide and sphingosine, as well as to other lipids (Fig. 1A). S1P and its metabolites control basic cell functions, such as proliferation, apoptosis, and migration, and are involved in several pathologic conditions, including inflammation, metabolic disease, and cancer (1, 2). Thus, insight into S1P metabolism and how this regulates its functional activity is of key importance in understanding the role of S1P in biology and disease. S1P is produced by the sphingosine kinase-dependent phosphorylation of sphingosine, which is created as a degradation product of ceramide (4). Within cells, S1P is degraded through two pathways, either by irreversible cleavage by S1P lyase (5) or by dephosphorylation by specific S1P phosphatases (SPPases) (also known as S1P phosphohydrolases) (6). When cleaved by S1P lyase (Sgpl1), phosphoethanolamine and hexadecenal are produced, which are then transferred as substrates from the sphingolipid pathway to the glycerophospholipid pathway.In an alternative catabolic route catalyzed by S1P phosphatases, the resulting sphingosine product can be derivatized with a fatty acid by ceramide synthase to produce cer...

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“…T ype II phosphatidic acid phosphatases (PAP2s) are a large family of phosphatases important for lipid metabolism and signaling (1,2). PAP2 proteins have been found in all life kingdoms from bacteria to mammals.…”

mentioning

confidence: 99%

Crystal structure of lipid phosphatase Escherichia coli phosphatidylglycerophosphate phosphatase B

Fan

Jiang

Zhao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Membrane-integrated type II phosphatidic acid phosphatases (PAP2s) are important for numerous bacterial to human biological processes, including glucose transport, lipid metabolism, and signaling. Escherichia coli phosphatidylglycerol-phosphate phosphatase B (ecPgpB) catalyzes removing the terminal phosphate group from a lipid carrier, undecaprenyl pyrophosphate, and is essential for transport of many hydrophilic small molecules across the membrane. We determined the crystal structure of ecPgpB at a resolution of 3.2 Å. This structure shares a similar folding topology and a nearly identical active site with soluble PAP2 enzymes. However, the substrate binding mechanism appears to be fundamentally different from that in soluble PAP2 enzymes. In ecPgpB, the potential substrate entrance to the active site is located in a cleft formed by a V-shaped transmembrane helix pair, allowing lateral movement of the lipid substrate entering the active site from the membrane lipid bilayer. Activity assays of point mutations confirmed the importance of the catalytic residues and potential residues involved in phosphate binding. The structure also suggests an induced-fit mechanism for the substrate binding. The 3D structure of ecPgpB serves as a prototype to study eukaryotic PAP2 enzymes, including human glucose-6-phosphatase, a key enzyme in the homeostatic regulation of blood glucose concentrations.T ype II phosphatidic acid phosphatases (PAP2s) are a large family of phosphatases important for lipid metabolism and signaling (1, 2). PAP2 proteins have been found in all life kingdoms from bacteria to mammals. They catalyze dephosphorylation of broad substrates by specifically hydrolyzing phosphoric monoester bonds. Their substrates include variety of phosphorylated carbohydrates, peptides, and lipids. PAP2s are involved in vesicular trafficking, secretion, and endocytosis (e.g., the enzyme phosphatidate phosphatase APP1 in yeast) (3); protein glycosylation [e.g., dolichyl pyrophosphate phosphatase 1 (DOLPP1) in the mouse] (4); energy storage (e.g., triacylglycerol biosynthesis) (5); and stress response (6). In contrast to type I PAP enzymes, which are Mg 2+ -dependent and usually soluble, PAP2 proteins are Mg 2+ -independent, and many of PAP2 enzymes are integral transmembrane (TM) proteins (7). Whereas the soluble branch of PAP2s is called class A nonspecific acid phosphatases (NSAPs) (8), the TM branch of the PAP2 family is also called the lipid phosphatase/phosphotransferase family (2) or lipid phosphate phosphatase family (9). Human glucose-6-phosphatase (G6Pase), the key enzyme in the homeostatic regulation of blood glucose concentrations, belongs to the TM PAP2 subfamily (10). Thus, the TM property is unique to the PAP2 family.In Escherichia coli, undecaprenyl phosphate (C 55 -P), a 55-carbon single-lipid chain phospholipid, serves as a carrier lipid to transfer a variety of phosphate-linked polymers across the periplasmic membrane from the cytosol to the periplasmic space. Recently, the crystal structure of phospho-N-acet...

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Integral membrane lipid phosphatases/phosphotransferases: common structure and diverse functions

Cited by 182 publications

References 100 publications

Lipid Phosphate Phosphatase-1 Regulates Lysophosphatidate-induced Fibroblast Migration by Controlling Phospholipase D2-dependent Phosphatidate Generation

Lipid Phosphate Phosphatase-1 Regulates Lysophosphatidate-induced Fibroblast Migration by Controlling Phospholipase D2-dependent Phosphatidate Generation

Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet β-Cell Endoplasmic Reticulum Stress and Proliferation

Crystal structure of lipid phosphatase Escherichia coli phosphatidylglycerophosphate phosphatase B

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