Role of sphingosine kinases and lipid phosphate phosphatases in regulating spatial sphingosine 1-phosphate signalling in health and disease

Pyne, Susan; Lee, Sue Chin; Long, Jaclyn; Pyne, Nigel J.

doi:10.1016/j.cellsig.2008.08.008

Cited by 117 publications

(73 citation statements)

References 103 publications

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“…These two enzymes exhibit different biochemical properties, are expressed in different tissues, are located in different subcellular compartments, and manifest distinct biological functions. S1P generated through the actions of sphingosine kinases can be dephosphorylated by the S1P phosphatases SPP1 and SPP2 or through reactions catalyzed by nonspecifi c lipid phosphate phosphatases, the LPPs (27)(28)(29). However, each of these reactions results in regeneration of sphingosine, which is then immediately available to be rephosphorylated.…”

Section: Whole Mount Survey Of Spl ␤ -Gal Reporter Expression In Adulmentioning

confidence: 99%

Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues

Borowsky

Bandhuvula²,

Kumar³

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org Sphingosine-1-phosphate (S1P) is the fi nal metabolic product of sphingolipid degradation. It circulates in the blood and lymph bound to lipoproteins and functions as a ligand for a family of fi ve differentially expressed G proteincoupled receptors, the S1P receptors (S1PRs) ( 1, 2 ). Acting through these receptors and the downstream signaling events mediated by them, S1P infl uences cell migration, survival, and stress responses ( 3 ). S1PR signaling is critical for development, as demonstrated by the embryonic lethal phenotype of S1PR1 knockout mice, due to severe hemorrhage associated with impaired vascular maturation ( 4 ). S1PR2 knockout mice are deaf due to defects in the stria vascularis ( 5 ). Additional studies have demonstrated the importance of S1P transport and signaling in cardiac and brain development, reproduction, and embryonic stem cell survival ( 6-17 ). S1P acts through its cognate receptors to control T, B, natural killer, and hematopoietic stem cell traffi cking as these cells emerge from bone marrow and thymus and transit peripheral lymphoid organs ( 18,19 ). S1P signaling contributes to the regulation and constitutive activation of key transcription factors that play a central role in infl ammation and cancer, including nuclear factor-B and STAT3 ( 20,21 ). S1P is also a mediator of cardioprotection in response to ischemia and can reduce developmental cell death as well as apoptosis, tissue injury, and infertility in response to ionizing radiation ( 22-24 ). Although many effects of S1P signaling are mediated through activation of its receptors, some of its actions, including activation of nuclear factor-B signaling and regulation of histone deacetylases, appear to be mediated through the receptor-independent, intracellular functions of S1P ( 21,25 ). S1P is generated via phosphorylation of the sphingoid base sphingosine by sphingosine kinases SphK1 and SphK2Abstract Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in immunity, infl ammation, angiogenesis, and cancer. S1P lyase (SPL) is the essential enzyme responsible for S1P degradation. SPL augments apoptosis and is down-regulated in cancer. SPL generates a S1P chemical gradient that promotes lymphocyte traffi cking and as such is being targeted to treat autoimmune diseases. Despite growing interest in SPL as a disease marker, antioncogene, and pharmacological target, no comprehensive characterization of SPL expression in mammalian tissues has been reported. We investigated SPL expression in developing and adult mouse tissues by generating and characterizing a ␤ -galactosidase-SPL reporter mouse combined with immunohistochemistry, immunoblotting, and enzyme assays. SPL was expressed in thymic and splenic stromal cells, splenocytes, Peyer's Patches, colonic lymphoid aggregates, circulating T and B lymphocytes, granulocytes, and monocytes, with lowest expression in thymocytes. SPL was highly expressed within the CNS, including arachnoid lining cells, spinal cord, ch...

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Section: Whole Mount Survey Of Spl ␤ -Gal Reporter Expression In Adulmentioning

confidence: 99%

Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues

Borowsky

Bandhuvula²,

Kumar³

et al. 2012

Journal of Lipid Research

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“…PAP2 are also known as lipid phosphate phosphatases (LPPs) because, in addition to PA, they can also catalyze in vitro the dephosphorylation of other lipid phosphates such as ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), and lysophosphatidic acid (LPA) with different affinities (PA ,LPA .C1P.S1P) Roberts et al, 1998;Waggoner et al, 1996). Due to the crucial role of the substrates and products of PAP activity in cell signaling, several PAP isoforms have been shown to contribute to the production of lipid signaling metabolites both inside and outside cells Pyne et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Lipid phosphate phosphatase 3 participates in transport carrier formation and protein trafficking in the early secretory pathway

Gutiérrez-Martínez

Fernández-Ulibarri

Lázaro‐Diéguez

et al. 2013

Journal of Cell Science

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SummaryThe inhibition of phosphatidic acid phosphatase (PAP) activity by propanolol indicates that diacylglycerol (DAG) is required for the formation of transport carriers at the Golgi and for retrograde trafficking to the ER. Here we report that the PAP2 family member lipid phosphate phosphatase 3 (LPP3, also known as PAP2b) localizes in compartments of the secretory pathway from ER export sites to the Golgi complex. The depletion of human LPP3: (i) reduces the number of tubules generated from the ER-Golgi intermediate compartment and the Golgi, with those formed from the Golgi being longer in LPP3-silenced cells than in control cells; (ii) impairs the Rab6-dependent retrograde transport of Shiga toxin subunit B from the Golgi to the ER, but not the anterograde transport of VSV-G or ssDsRed; and (iii) induces a high accumulation of Golgi-associated membrane buds. LPP3 depletion also reduces levels of de novo synthesized DAG and the Golgi-associated DAG contents. Remarkably, overexpression of a catalytically inactive form of LPP3 mimics the effects of LPP3 knockdown on Rab6-dependent retrograde transport. We conclude that LPP3 participates in the formation of retrograde transport carriers at the ER-Golgi interface, where it transitorily cycles, and during its route to the plasma membrane.

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“…S1P binds to a family of five G-protein-coupled receptors termed S1P n (where n ϭ 1 to 5), that are differentially coupled to heterotrimeric G-proteins to regulate various effectors, such as MAPKs, linked to diverse cellular processes (6). S1P is produced by sphingosine kinase (two isoforms termed SK1 and SK2) that catalyze the phosphorylation of sphingosine to produce S1P (28). SK1 is regulated by phosphorylation, catalyzed by extracellular signal regulated kinase 1/2 (ERK-1/2) (27) and has been demonstrated to increase Ras-dependent transformation of cancer cells (41), possibly via ERK-1/2-dependent targeting of SK1 to the plasma membrane of cells, and increase thereof of its so-called oncogenic function.…”

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confidence: 99%

Sphingosine Kinase 1 Induces Tolerance to Human Epidermal Growth Factor Receptor 2 and Prevents Formation of a Migratory Phenotype in Response to Sphingosine 1-Phosphate in Estrogen Receptor-Positive Breast Cancer Cells

Long

Edwards

Watson

et al. 2010

Molecular and Cellular Biology

133

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We demonstrate here a new concept termed "oncogene tolerance" whereby human EGF receptor 2 (HER2) increases sphingosine kinase 1 (SK1) expression in estrogen receptor-positive (ER ؉ ) MCF-7 HER2 cells and SK1, in turn, limits HER2 expression in a negative-feedback manner. The HER2-dependent increase in SK1 expression also limits p21-activated protein kinase 1 (p65 PAK1) and extracellular signal regulated kinase 1/2 (ERK-1/2) signaling. Sphingosine 1-phosphate signaling via S1P 3 is also altered in MCF-7 HER2 cells. In this regard, S1P binding to S1P 3 induces a migratory phenotype via an SK1-dependent mechanism in ER ؉ MCF-7 Neo cells, which lack HER2. This involves the S1P stimulated accumulation of phosphorylated ERK-1/2 and actin into membrane ruffles/lamellipodia and migration. In contrast, S1P failed to promote redistribution of phosphorylated ERK-1/2 and actin into membrane ruffles/lamellipodia or migration of MCF-7 HER2 cells. However, a migratory phenotype in these cells could be induced in response to S1P when SK1 expression had been knocked down with a specific siRNA or when recombinant PAK1 was ectopically overexpressed. Thus, the HER2-dependent increase in SK1 expression functions to desensitize the S1P-induced formation of a migratory phenotype. This is correlated with improved prognosis in patients who have a low HER1-3/SK1 expression ratio in their ER ؉ breast cancer tumors compared to patients that have a high HER1-3/SK1 expression ratio."Oncogene addiction" is a term that has been used to describe the reliance of cancer cells on the continued expression of oncogenes in order to maintain the diseased phenotype, progression, and metastasis of the cancer cell (39). Oncogene addiction is intrinsically susceptible to cross talk and feedback regulation that reflects abnormal signaling wiring in the cancer cell and which potentially makes these cells more susceptible to drug intervention at the level of the oncogene than normal cells. HER2 is a well-established oncogene that has an important role in enhancing breast cancer progression (2). The importance of its functional role as an addictive oncogene is exemplified by the fact that targeting HER2 with antibody mediated therapies, such as herceptin, demonstrates significant clinical efficacy (40). Indeed, this approach is in line with the concept that oncogene addiction is the "Achilles heel" of the cancer cell.There are four members of the human epidermal growth factor (EGF) receptor-related family, termed HER1 to HER4. The HER2/neu (c-erbB-2) gene encodes a 185-kDa transmembrane receptor tyrosine kinase, which is similar in amino acid sequence to other members of the EGF receptor family (30). Moreover, the overexpression of HER2/neu and gene amplification is found in up to 30% of primary breast cancers, and its expression is correlated with increased tumor invasion, poor prognosis, and therapeutic resistance (2). Overexpression of HER2 is also associated with downregulation of the estrogen receptor (ER) but not necessarily the complete elimination of...

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Role of sphingosine kinases and lipid phosphate phosphatases in regulating spatial sphingosine 1-phosphate signalling in health and disease

Cited by 117 publications

References 103 publications

Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues

Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues

Lipid phosphate phosphatase 3 participates in transport carrier formation and protein trafficking in the early secretory pathway

Sphingosine Kinase 1 Induces Tolerance to Human Epidermal Growth Factor Receptor 2 and Prevents Formation of a Migratory Phenotype in Response to Sphingosine 1-Phosphate in Estrogen Receptor-Positive Breast Cancer Cells

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