Co-ordinate regulation of growth factor receptors and lipid phosphate phosphatase-1 controls cell activation by exogenous lysophosphatidate

2001 ◽  
Vol 29 (6) ◽  
pp. 825-830 ◽  
Author(s):  
C. Pilquil ◽  
Z.-C. Ling ◽  
I. Singh ◽  
K. Buri ◽  
Q.-X. Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Activation ◽  
Growth Factor Receptors ◽  
Exogenous Lipid ◽  
Edg Receptors ◽  
Sphingosine 1 Phosphate ◽  
Lipid Phosphate ◽  
Lipid Phosphate Phosphatases ◽  
Differentiation Gene

The serum-derived lipid growth factors, lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P), activate cells selectively through different members of a family of endothelial differentiation gene (EDG) receptors. Activation of EDG receptors by LPA and S1P provides a variety of signalling cascades depending upon the G-protein coupling of the different EDG receptors. This leads to chemotactic and mitogenic responses, which are important in wound healing. For example, LPA stimulates fibroblast division and S1P stimulates the chemotaxis and division of endothelial cells leading to angiogenesis. Counteracting these effects of LPA and S1P, are the actions of lipid phosphate phosphatases (LPP, or phosphatidate phosphohydrolases, Type 2). The isoform LPP-1 is expressed in the plasma membrane with its active site outside the cell. This enzyme is responsible for ‘ecto-phosphatase’ activity leading to the degradation of exogenous lipid phosphate mediators, particularly LPA. Expression of LPP-1 decreases cell activation by exogenous LPA. The mechanism for this is controversial and several mechanisms have been proposed. Evidence will be presented that the LPPs cross-talk with EDG and other growth factor receptors, thus, regulating the responses of the cells to lipid phosphate mediators of signal transduction.

Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

2014 ◽  
Vol 326 (1) ◽  
pp. 112-124 ◽  
Author(s):  
Yosuke Nagata ◽  
Kazuya Ohashi ◽  
Eiji Wada ◽  
Yuki Yuasa ◽  
Masataka Shiozuka ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Satellite Cell ◽  
Cell Activation ◽  
Muscle Satellite Cell ◽  
Sphingosine 1 Phosphate ◽  
Satellite Cell Activation ◽  
Epidermal Growth

scholarly journals Lipid phosphate phosphatases form homo- and hetero-oligomers: catalytic competency, subcellular distribution and function

2008 ◽  
Vol 411 (2) ◽  
pp. 371-377 ◽  
Author(s):  
Jaclyn S. Long ◽  
Nigel J. Pyne ◽  
Susan Pyne
Keyword(s):  
Recombinant Expression ◽  
Catalytic Site ◽  
Wild Type ◽  
Catalytically Active ◽  
Exclusion Chromatography ◽  
Sphingosine 1 Phosphate ◽  
Lipid Phosphate ◽  
Extracellular Side ◽  
And Function ◽  
Lipid Phosphate Phosphatases

Lipid phosphate phosphatases (LPP1–LPP3) have been topographically modelled as monomers (molecular mass of 31–36 kDa) composed of six transmembrane domains and with the catalytic site facing the extracellular side of the plasma membrane or the luminal side of intracellular membranes. The catalytic motif has three conserved domains, termed C1, C2 and C3. The C1 domain may be involved in substrate recognition, whereas C2 and C3 domains appear to participate in the catalytic dephosphorylation of the substrate. We have obtained three lines of evidence to demonstrate that LPPs exist as functional oligomers. First, we have used recombinant expression and immunoprecipitation analysis to demonstrate that LPP1, LPP2 and LPP3 form both homo- and hetero-oligomers. Secondly, large LPP oligomeric complexes that are catalytically active were isolated using gel-exclusion chromatography. Thirdly, we demonstrate that catalytically deficient guinea-pig FLAG-tagged H223L LPP1 mutant can form an oligomer with wild-type LPP1 and that wild-type LPP1 activity is preserved in the oligomer. These findings suggest that, in an oligomeric arrangement, the catalytic site of the wild-type LPP can function independently of the catalytic site of the mutant LPP. Finally, we demonstrate that endogenous LPP2 and LPP3 form homo- and hetero-oligomers, which differ in their subcellular localization and which may confer differing spatial regulation of phosphatidic acid and sphingosine 1-phosphate signalling.

Lipid phosphate phosphatases and lipid phosphate signalling

2005 ◽  
Vol 33 (6) ◽  
pp. 1370-1374 ◽  
Author(s):  
S. Pyne ◽  
J.S. Long ◽  
N.T. Ktistakis ◽  
N.J. Pyne
Keyword(s):  
Physiological Role ◽  
Mitogen Activated Protein Kinase ◽  
Hek 293 ◽  
Lipid Phosphatases ◽  
Mitogen Activated Protein ◽  
Phospholipase D1 ◽  
Sphingosine 1 Phosphate ◽  
Lipid Phosphate ◽  
Lipid Phosphate Phosphatases

Mammalian LPPs (lipid phosphate phosphatases) are integral membrane proteins that belong to a superfamily of lipid phosphatases/phosphotransferases. They have broad substrate specificity in vitro, dephosphorylating PA (phosphatidic acid), S1P (sphingosine 1-phosphate), LPA (lysophosphatidic acid) etc. Their physiological role may include the attenuation of S1P- and LPA-stimulated signalling by virtue of an ecto-activity (i.e. dephosphorylation of extracellular S1P and LPA), thereby limiting the activation of LPA- and S1P-specific G-protein-coupled receptors at the cell surface. However, our recent work suggests that an intracellular action of LPP2 and LPP3 may account for the reduced agonist-stimulated p42/p44 mitogen-activated protein kinase activation of HEK-293 (human embryonic kidney 293) cells. This may involve a reduction in the basal levels of PA and S1P respectively and the presence of an early apoptotic phenotype under conditions of stress (serum deprivation). Additionally, we describe a model whereby LPP2, but not LPP3, may be functionally linked to the phospholipase D1-derived PA-dependent recruitment of sphingosine kinase 1 to the perinuclear compartment. We also consider the potential regulatory mechanisms for LPPs, which may involve oligomerization. Lastly, we highlight many aspects of the LPP biology that remain to be fully defined.

scholarly journals Sphingosine 1-phosphate induces Ca2+ transients and cytoskeletal rearrangement in C2C12 myoblastic cells

2002 ◽  
Vol 282 (6) ◽  
pp. C1361-C1373 ◽  
Author(s):  
Lucia Formigli ◽  
Fabio Francini ◽  
Elisabetta Meacci ◽  
Massimo Vassalli ◽  
Daniele Nosi ◽  
...  
Keyword(s):  
Specific Inhibitor ◽  
Cell Contraction ◽  
Cytoskeletal Rearrangement ◽  
Edg Receptors ◽  
Inositol 1,4,5 Trisphosphate ◽  
Confocal Fluorescence ◽  
Sphingosine 1 Phosphate ◽  
Intracellular Ca ◽  
Confocal Fluorescence Imaging ◽  
Differentiation Gene

In many cell systems, sphingosine 1-phosphate (SPP) increases cytosolic Ca2+concentration ([Ca2+]i) by acting as intracellular mediator and extracellular ligand. We recently demonstrated (Meacci E, Cencetti F, Formigli L, Squecco R, Donati C, Tiribilli B, Quercioli F, Zecchi-Orlandini S, Francini F, and Bruni P. Biochem J 362: 349–357, 2002) involvement of endothelial differentiation gene (Edg) receptors (Rs) specific for SPP in agonist-mediated Ca2+ response of a mouse skeletal myoblastic (C2C12) cell line. Here, we investigated the Ca2+ sources of SPP-mediated Ca2+ transients in C2C12 cells and the possible correlation of ion response to cytoskeletal rearrangement. Confocal fluorescence imaging of C2C12 cells preloaded with Ca2+ dye fluo 3 revealed that SPP elicited a transient Ca2+ increase propagating as a wave throughout the cell. This response required extracellular and intracellular Ca2+ pool mobilization. Indeed, it was significantly reduced by removal of external Ca2+, pretreatment with nifedipine (blocker of L-type plasma membrane Ca2+channels), and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-mediated Ca2+pathway inhibitors. Involvement of EdgRs was tested with suramin (specific inhibitor of Edg-3). Fluorescence associated with Ins(1,4,5)P3Rs and L-type Ca2+channels was evident in C2C12 cells. SPP also induced C2C12 cell contraction. This event, however, was unrelated to [Ca2+]i increase, because the two phenomena were temporally shifted. We propose that SPP may promote C2C12 cell contraction through Ca2+-independent mechanisms.

scholarly journals Lipid Phosphate Phosphatases and Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1263 ◽  
Author(s):  
Xiaoyun Tang ◽  
David N. Brindley
Keyword(s):  
Endoplasmic Reticulum ◽  
Cancer Progression ◽  
Plasma Membranes ◽  
Wide Spectrum ◽  
Integral Membrane Proteins ◽  
Extracellular Signaling ◽  
Sphingosine 1 Phosphate ◽  
Lipid Phosphate ◽  
Golgi Network ◽  
Lipid Phosphate Phosphatases

Lipid phosphate phosphatases (LPPs) are a group of three enzymes (LPP1–3) that belong to a phospholipid phosphatase (PLPP) family. The LPPs dephosphorylate a wide spectrum of bioactive lipid phosphates, among which lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P) are two important extracellular signaling molecules. The LPPs are integral membrane proteins, which are localized on plasma membranes and intracellular membranes, including the endoplasmic reticulum and Golgi network. LPPs regulate signaling transduction in cancer cells and demonstrate different effects in cancer progression through the breakdown of extracellular LPA and S1P and other intracellular substrates. This review is intended to summarize an up-to-date understanding about the functions of LPPs in cancers.

Sign in / Sign up

Export Citation Format

Share Document