Structural organization of mammalian lipid phosphate phosphatases: implications for signal transduction

Waggoner, David W.; Xu, James; Singh, Indrapal N.; Jasińska, Renata; Zhang, Qiuxia; Brindley, David N.

doi:10.1016/s1388-1981(99)00102-x

Cited by 127 publications

(125 citation statements)

References 98 publications

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“…As indicated above, present evidence, albeit circumstantial, indicates LPP does not have access to LPA or PA generated during de novo glycerolipid synthesis via the Kennedy pathway (22,194,260) (Fig. 1).…”

Section: Substrates For Lppsupporting

confidence: 52%

“…PA can also be hydrolyzed to LPA and considerable evidence has accumulated implicating LPA as an extracellular messenger (18,46,113,139,156,260). However, as in the case of S1P, caution is advised, and the evidence for a role for LPA or PA itself should be examined for each case.…”

Section: As Indicated In Substrates Formentioning

confidence: 99%

“…Originally considered only for its role in glycerolipid biosynthesis, it has recently been demonstrated that this phosphohydrolase plays an important role as a modulator of cell signaling in relation to cell mobility, differentiation, growth, and survival (24,25,31,120,260).…”

mentioning

confidence: 99%

“…Unlike PAP1, which is highly specific for the Mg 2ϩ salts of PA and LPA, PAP2 degrades a number of lipid phosphates, including S1P, ceramide-1-phosphate (C1P), as well as PA and LPA, does not require specific ions, and is heat and sulphhydryl reagent resistant. It has consequently been suggested that PAP2 be designated lipid phosphate phosphatase (LPP) (25,107,260).…”

mentioning

confidence: 99%

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Pulmonary phosphatidic acid phosphatase and lipid phosphate phosphohydrolase

Nanjundan

Possmayer

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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The lung contains two distinct forms of phosphatidic acid phosphatase (PAP). PAP1 is a cytosolic enzyme that is activated through fatty acid-induced translocation to the endoplasmic reticulum, where it converts phosphatidic acid (PA) to diacylglycerol (DAG) for the biosynthesis of phospholipids and neutral lipids. PAP1 is Mg2+ dependent and sulfhydryl reagent sensitive. PAP2 is a six-transmembrane-domain integral protein localized to the plasma membrane. Because PAP2 degrades sphingosine-1-phosphate (S1P) and ceramide-1-phosphate in addition to PA and lyso-PA, it has been renamed lipid phosphate phosphohydrolase (LPP). LPP is Mg2+independent and sulfhydryl reagent insensitive. This review describes LPP isoforms found in the lung and their location in signaling platforms (rafts/caveolae). Pulmonary LPPs likely function in the phospholipase D pathway, thereby controlling surfactant secretion. Through lowering the levels of lyso-PA and S1P, which serve as agonists for endothelial differentiation gene receptors, LPPs regulate cell division, differentiation, apoptosis, and mobility. LPP activity could also influence transdifferentiation of alveolar type II to type I cells. It is considered likely that these lipid phosphohydrolases have critical roles in lung morphogenesis and in acute lung injury and repair.

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Section: Substrates For Lppsupporting

confidence: 52%

Section: As Indicated In Substrates Formentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Pulmonary phosphatidic acid phosphatase and lipid phosphate phosphohydrolase

Nanjundan

Possmayer

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In addition to its substrate specificity, which distinguishes mSPP1 from the previously cloned type 2 phosphohydrolases, the sequence of mSPP1 is more similar to the yeast SPP phosphatases than to mammalian LPPs: SPP phosphatases are larger, consisting of 404-430 aa as compared with 281-312 aa; hydrophobicity plots predict 8-10 potential membrane-spanning domains in SPP phosphatases, in contrast to six well-defined transmembrane domains found in LPPs; and mSPP1 has one potential glycosylation site that is not conserved in the yeast orthologs and is predicted to be located on the opposite side of the membrane from the catalytic domains, unlike the LPPs, where the catalytic domains and glycosylation site are predicted to be in the first and second extracellular loops. Several experimental approaches have supported a topological model in which the N and C termini of LPPs are present at the cytosolic surface, and the active site and glycosylation site are exposed at the extracellular membrane surface (49). Consistent with a model of ecto-phosphatase activity is the finding that cells expressing LPP1 showed enhanced degradation of exogenous LPA and attenuated LPAmediated activation of both the extracellular signal-regulated kinase pathway and DNA synthesis (48).…”

Section: Discussionmentioning

confidence: 76%

Molecular cloning and characterization of a lipid phosphohydrolase that degrades sphingosine-1- phosphate and induces cell death

Mandala

Thornton

Galve‐Roperh

et al. 2000

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

188

143

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Sphingosine and sphingosine-1-phosphate (SPP) are interconvertible sphingolipid metabolites with opposing effects on cell growth and apoptosis. Based on sequence homology with LBP1, a lipid phosphohydrolase that regulates the levels of phosphorylated sphingoid bases in yeast, we report here the cloning, identification, and characterization of a mammalian SPP phosphatase (mSPP1). This hydrophobic enzyme, which contains the type 2 lipid phosphohydrolase conserved sequence motif, shows substrate specificity for SPP. Partially purified Myc-tagged mSPP1 was also highly active at dephosphorylating SPP. When expressed in yeast, mSPP1 can partially substitute for the function of LBP1. Membrane fractions from human embryonic kidney HEK293 cells transfected with mSPP1 markedly degraded SPP but not lysophosphatidic acid, phosphatidic acid, or ceramide-1-phosphate. Enforced expression of mSPP1 in NIH 3T3 fibroblasts not only decreased SPP and enhanced ceramide levels, it also markedly diminished survival and induced the characteristic traits of apoptosis. Collectively, our results suggest that SPP phosphohydrolase may regulate the dynamic balance between sphingolipid metabolite levels in mammalian cells and consequently influence cell fate.S phingosine-1-phosphate (SPP) is a bioactive sphingolipid metabolite that regulates diverse biological processes (reviewed in refs. 1 and 2). Many of its pleiotropic actions appear to be mediated by a family of specific cell surface G proteincoupled receptors (GPCR), known as EDG (endothelial differentiation genes) receptors. Binding of SPP to EDG-1 expressed on endothelial cells enhances survival (3), chemotaxis, and in vitro angiogenesis (4), and adherens junction assembly leading to morphogenetic differentiation (5), whereas binding of SPP to EDG-5 and EDG-3 induces neurite retraction and soma rounding (6, 7). SPP induces activation of G i -gated inward rectifying K ϩ -channels in atrial myocytes (8) and inhibits motility of melanoma cells (9) through as yet uncharacterized GPCRs.SPP also plays important roles inside cells. In response to diverse external stimuli, sphingosine kinase, the enzyme that catalyzes the phosphorylation of sphingosine to SPP, is activated (10-15). Intracellular SPP, in turn, mobilizes calcium from internal stores independently of inositol triphosphate (15, 16), as well as eliciting diverse signaling pathways leading to proliferation (17, 18) and suppression of apoptosis (19)(20)(21)(22).Because of its dual function as a ligand and second messenger and its pivotal role in cell growth and survival, the synthesis and degradation of SPP should be tightly regulated in a spatialtemporal manner. Until recently, however, little was known of the enzymes involved in SPP metabolism. We have purified sphingosine kinase to apparent homogeneity from rat kidney (23) and subsequently cloned and characterized a mammalian sphingosine kinase (24), which belongs to a highly conserved gene family (24,25). Enforced expression of sphingosine kinase markedly enhanced proliferation a...

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Vanadium Haloperoxidases

Wever¹,

Hemrika²

2004

Handbook of Metalloproteins

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This chapter describes the occurrence and the biological function of the vanadium bromoperoxidases and chloroperoxidases. These enzymes that contain vanadate as the prosthetic group catalyze the oxidation of halides to the corresponding hypohalous acids. Purification and molecular characterization of these enzymes is reported and a detailed comparison is made between a bromoperoxidase and a chloroperoxidase, both kinetically as well as structurally. The vanadate‐binding site in haloperoxidases shows an interesting homology with the binding site of phosphate in a large group of phosphatases. Finally, on the basis of mutagenesis studies, a catalytic mechanism is presented for the vanadium chloroperoxidase activity that details the role in catalysis of the amino acid residues in the first coordination sphere of the metal oxide.

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Structural organization of mammalian lipid phosphate phosphatases: implications for signal transduction

Cited by 127 publications

References 98 publications

Pulmonary phosphatidic acid phosphatase and lipid phosphate phosphohydrolase

Pulmonary phosphatidic acid phosphatase and lipid phosphate phosphohydrolase

Molecular cloning and characterization of a lipid phosphohydrolase that degrades sphingosine-1- phosphate and induces cell death

Vanadium Haloperoxidases

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