Sphingosine kinase 1 localized to the plasma membrane lipid raft microdomain overcomes serum deprivation induced growth inhibition

Hengst, Jeremy A.; Guilford, Jacquelyn; Fox, Todd E.; Wang, Xujun; Conroy, Elizabeth J; Yun, Jong K.

doi:10.1016/j.abb.2009.09.013

Cited by 46 publications

(50 citation statements)

References 59 publications

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“…The lack of HSP70BЈ protein suggested aborted translation, improper folding, and/or complexing to an undetermined molecule(s) concealing the antibody binding sites. Due to cross-linking of the Fc␥ receptors with immune complexes (oxLDL-IC and KLH-IC), we believe that the HSP70BЈ protein and possibly other stimulated proteins, such as SK1 (18,37), become part of lipid rafts and/or the detergent-resistant membrane fraction. To extract the cell membrane-associated HSP70BЈ, which is dem- onstrated clearly in the confocal microscopy images, we used several different detergents and extraction buffers (38) (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Protein 70B′ (HSP70B′) Expression and Release in Response to Human Oxidized Low Density Lipoprotein Immune Complexes in Macrophages

Smith

Twal

Soodavar

et al. 2010

Journal of Biological Chemistry

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Heat shock proteins (HSPs) have been implicated in the activation and survival of macrophages. This study examined the role of HSP70B, a poorly characterized member of the HSP70 family, in response to oxidatively modified LDL (oxLDL) and immune complexes prepared with human oxLDL and purified human antibodies to oxLDL (oxLDL-IC) in monocytic and macrophage cell lines. Immunoblot analysis of cell lysates and conditioned medium from U937 cells treated with oxLDL alone revealed an increase in intracellular HSP70B protein levels accompanied by a concomitant increase in HSP70B extracellular levels. Fluorescence immunohistochemistry and confocal microscopy, however, demonstrated that oxLDL-IC stimulated the release of HSP70B, which co-localized with cell-associated oxLDL-IC. In HSP70B-green fluorescent protein-transfected mouse RAW 264.7 cells, oxLDL-IC-induced HSP70B co-localized with membrane-associated oxLDL-IC as well as the lipid moiety of internalized oxLDL-IC. Furthermore, the data demonstrated that HSP70B is involved in cell survival, and this effect could be mediated by sphingosine kinase 1 (SK1) activation. An examination of regularly implicated cytokines revealed a significant relationship between HSP70B and the release of the anti-inflammatory cytokine interleukin-10 (IL-10). Small interfering RNA knockdown of HSP70B resulted in a corresponding decrease in SK1 mRNA levels and SK1 phosphorylation as well as increased release of IL-10. In conclusion, these findings suggest that oxLDL-IC induce the synthesis and release of HSP70B, and once stimulated, HSP70B binds to the cellassociated and internalized lipid moiety of oxLDL-IC. The data also implicate HSP70B in key cellular functions, such as regulation of SK1 activity and release of IL-10, which influence macrophage activation and survival.

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Section: Discussionmentioning

confidence: 99%

Heat Shock Protein 70B′ (HSP70B′) Expression and Release in Response to Human Oxidized Low Density Lipoprotein Immune Complexes in Macrophages

Smith

Twal

Soodavar

et al. 2010

Journal of Biological Chemistry

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“…After centrifugation (100,000g, 15 min) to remove insoluble material, protein content of each lysate was determined using the BCA protein assay (Pierce). Lysates prepared as described contained both cytosolic and membrane-associated SphK1 [32]. Lysate samples containing 25 lg of protein were combined with 25 lM D-erythro-sphingosine, 10 mM MgCl 2 , 2 lM ATP and 2 lCi [c- 32 …”

Section: Analysis Of Sphingosine Kinase 1 (Sphk1) Activitymentioning

confidence: 99%

Effect of HFE Variants on Sphingolipid Expression by SH-SY5Y Human Neuroblastoma Cells

et al. 2011

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C282Y and H63D are two common variants of the hemochromatosis protein HFE. SH-SY5Y human neuroblastoma cells stably transfected to express either wild type HFE (WT-HFE), or the C282Y or H63D allele were analyzed for effect of expression of the mutant proteins on transcription of 14 enzymes involved in sphingolipid metabolism. Cells expressing the C282Y variant showed significant increases (>2-fold) in transcription of five genes and decreases in two compared to that seen for cells expressing WT-HFE, while cells expressing the H63D variant showed an elevation in transcription of one gene and a decrease in two. These changes were seen as alterations in ganglioside composition, cell surface binding by the binding subunit of cholera toxin, expression of sphingosine-kinase-1 and synthesis of sphingosine-1-phosphate. These changes may explain why C282Y-HFE is a risk factor for colon and breast cancer and possibly protective against Alzheimer's disease while H63D-HFE is a risk factor for neurodegenerative diseases.

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“…Depending on the cellular context, SK1 may translocate to the caveolin-1 enriched domains in PM upon activation [23]. This PM translocation of SK1 is in part mediated by Ca 2+ [24] and may facilitate S1P secretion to the cell exterior, leading to autocrine S1P signaling [5,[24][25][26].…”

Section: Introductionmentioning

confidence: 99%

A novel chimeric aequorin fused with caveolin-1 reveals a sphingosine kinase 1-regulated Ca2+ microdomain in the caveolar compartment

Pulli

Blom

Löf

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Caveolae are plasma membrane invaginations enriched in sterols and sphingolipids. Sphingosine kinase 1 (SK1) is an oncogenic protein that converts sphingosine to sphingosine 1-phosphate (S1P), which is a messenger molecule involved in calcium signaling. Caveolae contain calcium responsive proteins, but the effects of SK1 or S1P on caveolar calcium signaling have not been investigated. We generated a Caveolin-1-Aequorin fusion protein (Cav1-Aeq) that can be employed for monitoring the local calcium concentration at the caveolae ([Ca²⁺]cav). In HeLa cells, Cav1-Aeq reported different [Ca²⁺] as compared to the plasma membrane [Ca²⁺] in general (reported by SNAP25-Aeq) or as compared to the cytosolic [Ca²⁺] (reported by cyt-Aeq). The Ca²⁺ signals detected by Cav1-Aeq were significantly attenuated when the caveolar structures were disrupted by methyl-β-cyclodextrin, suggesting that the caveolae are specific targets for Ca²⁺ signaling. HeLa cells overexpressing SK1 showed increased [Ca²⁺]cav during histamine-induced Ca²⁺ mobilization in the absence of extracellular Ca²⁺ as well as during receptor-operated Ca²⁺ entry (ROCE). The SK1-induced increase in [Ca²⁺]cav during ROCE was reverted by S1P receptor antagonists. In accordance, pharmacologic inhibition of SK1 reduced the [Ca²⁺]cav during ROCE. S1P treatment stimulated the [Ca²⁺]cav upon ROCE. The Ca²⁺ responses at the plasma membrane in general were not affected by SK1 expression. In summary, our results show that SK1/S1P-signaling regulates Ca²⁺ signals at the caveolae. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.

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Sphingosine kinase 1 localized to the plasma membrane lipid raft microdomain overcomes serum deprivation induced growth inhibition

Cited by 46 publications

References 59 publications

Heat Shock Protein 70B′ (HSP70B′) Expression and Release in Response to Human Oxidized Low Density Lipoprotein Immune Complexes in Macrophages

Heat Shock Protein 70B′ (HSP70B′) Expression and Release in Response to Human Oxidized Low Density Lipoprotein Immune Complexes in Macrophages

Effect of HFE Variants on Sphingolipid Expression by SH-SY5Y Human Neuroblastoma Cells

A novel chimeric aequorin fused with caveolin-1 reveals a sphingosine kinase 1-regulated Ca2+ microdomain in the caveolar compartment

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