Cell migration activated by platelet‐derived growth factor receptor is blocked by an inverse agonist of the sphingosine 1‐phosphate receptor‐1

Waters, Catherine; Long, Jaclyn; Горшкова, И. А.; Fujiwara, Yuko; Connell, Michelle; Belmonte, Kristen E.; Tigyi, Gábor; Natarajan, Viswanathan; Pyne, Susan; Pyne, Nigel J.

doi:10.1096/fj.05-4810fje

Cited by 76 publications

(80 citation statements)

References 32 publications

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“…Similar apparently conflicting data exist for the PDGF receptor. Although some evidence suggests that PDGF activates SK1 and causes S1P-dependent S1P receptor activation (36), other data suggest that crosstalk between PDGF and S1P receptors occurs in the context of a physical complex between the two receptors (37,54,55). Whichever model is ultimately correct, both incorporate the notion that a heptahelical S1P receptor functions as an intermediate in PDGF receptor-mediated G protein activation.…”

Section: Discussionmentioning

confidence: 99%

Insulin-like Growth Factors Mediate Heterotrimeric G Protein-dependent ERK1/2 Activation by Transactivating Sphingosine 1-Phosphate Receptors

El‐Shewy¹,

Johnson²,

Lee³

et al. 2006

J. Biol. Chem.

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Although several studies have shown that a subset of insulin-like growth factor (IGF) signals require the activation of heterotrimeric G proteins, the molecular mechanisms underlying IGF-stimulated G protein signaling remain poorly understood. Here, we have studied the mechanism by which endogenous IGF receptors activate the ERK1/2 mitogen-activated protein kinase cascade in HEK293 cells. In these cells, treatment with pertussis toxin and expression of a G␣ q/11 -(305-359) peptide that inhibits G q/11 signaling additively inhibited IGF-stimulated ERK1/2 activation, indicating that the signal was almost completely G protein-dependent. Treatment with IGF-1 or IGF-2 promoted translocation of green fluorescent protein (GFP)-tagged sphingosine kinase (SK) 1 from the cytosol to the plasma membrane, increased endogenous SK activity within 30 s of stimulation, and caused a statistically significant increase in intracellular and extracellular sphingosine 1-phosphate (S1P) concentration. Using a GFP-tagged S1P 1 receptor as a biological sensor for the generation of physiologically relevant S1P levels, we found that IGF-1 and IGF-2 induced GFP-S1P receptor internalization and that the effect was blocked by pretreatment with the SK inhibitor, dimethylsphingosine. Treating cells with dimethylsphingosine, silencing SK1 expression by RNA interference, and blocking endogenous S1P receptors with the competitive antagonist VPC23019 all significantly inhibited IGF-stimulated ERK1/2 activation, suggesting that IGFs elicit G protein-dependent ERK1/2 activation by stimulating SK1-dependent transactivation of S1P receptors. Given the ubiquity of SK and S1P receptor expression, S1P receptor transactivation may represent a general mechanism for G protein-dependent signaling by non-G protein-coupled receptors.The insulin-like growth factors type 1 and 2 (IGF-1 and -2) 2 are single chain polypeptides that share structural homology with proinsulin. The actions of IGF-1 and IGF-2 are mediated by binding to two structurally distinct plasma membrane receptors, referred to as the IGF-1 and IGF-2/mannose 6-phosphate (M6P) receptors. Most of the metabolic and mitogenic effects of IGF-1 and IGF-2 are thought to result from binding to the IGF-1 receptor, a receptor tyrosine kinase with structural homology to the insulin receptor. It is composed of two extracellular ␣ subunits and two transmembrane ␤ subunits linked by disulfide bonds (1, 2). Ligand binding to the ␣ subunits activates the intrinsic ␤ subunit receptor tyrosine kinase activity, leading to tyrosine phosphorylation of adapter proteins, such as insulin receptor substrate 1 (IRS-1) and Shc and Gab1 (3-6). Subsequent src homology 2 or protein tyrosine-binding domaindependent recruitment of enzymes with phospholipase, phosphatase, and protein and lipid kinase activity transmits signals intracellularly, including activation of the mitogenic Ras cascade and initiation of phosphatidylinositol 3-kinase (PI3K)/Aktdependent cell survival. Adding to the diversity, in some cell types IGF-1 stimula...

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Section: Discussionmentioning

confidence: 99%

Insulin-like Growth Factors Mediate Heterotrimeric G Protein-dependent ERK1/2 Activation by Transactivating Sphingosine 1-Phosphate Receptors

El‐Shewy¹,

Johnson²,

Lee³

et al. 2006

J. Biol. Chem.

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“…There is also some evidence supporting a model in which cross-talk is mediated by stable S1P receptor-tyrosine kinase receptor complexes (51)(52)(53). Receptor complexes consisting of PDGFb and a constitutively active S1P 1 have been shown to form independently of stimulation with either PDGF or S1P in several cell types, including HEK 293, airway smooth muscle cells, and fibroblasts (51)(52)(53).…”

Section: Receptor-receptor Interactionsmentioning

confidence: 94%

“…Receptor complexes consisting of PDGFb and a constitutively active S1P 1 have been shown to form independently of stimulation with either PDGF or S1P in several cell types, including HEK 293, airway smooth muscle cells, and fibroblasts (51)(52)(53). When these cells are stimulated with PDGF, the complex of receptors is endocytosed in a c-Src/b-arrestin-dependent fashion.…”

Section: Receptor-receptor Interactionsmentioning

confidence: 99%

“…The endocytosed complex associates with and activates ERK1/2. Inhibition of S1P 1 blocks both PDGFinduced activation of ERK1/2 and cell migration (53). In contrast to the models invoking activation of SphK1 and generation of S1P, which potentially provide a general mechanism for linking receptor tyrosine kinases to GPCR activation, to date this platform model has only been shown to be relevant to cross-talk between the PDGF and S1P signaling pathways.…”

Section: Receptor-receptor Interactionsmentioning

confidence: 99%

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Thematic Review Series: Sphingolipids. Cross-talk at the crossroads of sphingosine-1-phosphate, growth factors, and cytokine signaling*

Lebman

Spiegel

2008

Journal of Lipid Research

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Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that mediates a wide array of biologic effects through its interaction with a family of five G protein-coupled receptors. Cytokines and growth factors interact with this signaling pathway in a variety of ways, including both activation and regulation of the expression of the enzymes that regulate synthesis and degradation of S1P. Not only do many growth factors and cytokines stimulate S1P production, leading to transactivation of S1P receptors, ligation of S1P receptors by S1P can also transactivate growth factor tyrosine kinase receptors and stimulate growth factor and cytokine signaling cascades. This review discusses the mechanisms involved in cross-talk between S1P, cytokines, and growth factors and the impact of that cross-talk on cell signaling and cell biology. The biological effects of sphingosine-1-phosphate (S1P) overlap with those of a wide array of cytokines and growth factors. There is increasing evidence that this overlap in functions relates to both the ability of growth factors and cytokines to transactivate S1P signaling cascades as well as the ability of S1P to transactivate growth factor and cytokine signaling cascades. This mutual pathway cross-talk affects cell growth, differentiation, and movement and is integral to a variety of normal processes as well as disease processes, including inflammation and cancer. This review will focus on the ways in which S1P and growth factor or cytokine signaling pathways interact. S1P S1P is a potent bioactive lipid that regulates processes that are essential to cellular homeostasis, including cell viability, differentiation, and motility (1-3). Most of its bestcharacterized actions are mediated through a family of five G protein-coupled receptors, (GPCRs) S1P 1-5 (4, 5). The S1P receptors couple to a variety of G proteins, allowing them to mediate many different biologic responses (6, 7).One mechanism for cross-talk between cytokine or growth factor pathways and S1P signaling involves regulation of S1P metabolism. Sphingolipid metabolism was the focus of a recent excellent review (3) and will not be discussed in detail here. Cellular levels of S1P are regulated by the activities of the enzymes that are responsible for its synthesis and degradation. In mammalian cells, two sphingosine kinases, SphK1 and SphK2, catalyze the phosphorylation of sphingosine to generate S1P (8). Although both isozymes phosphorylate sphingosine, they differ in their enzymatic properties, cellular location, and biological roles (9). SphK1 is generally regarded as providing pro-survival signals, whereas SphK2, at least when overexpressed, induces apoptosis in several cell types (10). S1P is degraded to sphingosine by specific S1P phosphatases (11) or cleaved to palmitaldehyde and phosphoethanolamine by S1P lyase (12). Thus, it is clear that S1P levels can potentially be altered by stimuli that affect activity or expression of any of these enzymes. However, the majority of cytokines and growth factors that coopt regu...

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“…Phosphorylated ERK accumulates into membrane ruffles/lamellipodia and the nucleus and promotes migration of the cell. In the membrane ruffles, activated ERK promotes migration through the regulation of the actomyosin contractility while nuclear phosphorylated ERK enables cell movement by inducing metalloproteinase genes that are responsible for proteolytic degradation of the cell matrix [57,67]. Together, these studies suggest SphK1 activation by Estradiol induces S1P release and subsequent binding to S1P 3 , which sustains cytosomal EGFR and ERK activities to promote MCF-7 cells migration.…”

Section: Luminal A: Er/pr-positive and Her2-negativementioning

confidence: 89%

Involvement of Sphingosine Kinases/Sphingosine-1-Phosphate (S1P)/S1P Receptors in Breast Cancer Subtypes

2013

J Oncobiomark

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There is emerging evidence suggesting sphingolipids as critical regulators of cancer development and progression. Sphingolipids are potent bioactive lipids involved in fundamental biological processes including cell proliferation, apoptosis, angiogenesis, senescence, stress response and transformation. Ceramide, sphingosine and Sphingosine-1-phosphate (S1P) are inter-convertible sphingolipids with opposing effects on cell fate. Furthermore, S1P either acts directly on intracellular targets or through G-protein coupled S1PRs (S1P1-5) to mediate their specific effects. This review will discuss the roles of key sphingolipids, sphingosine kinases (SphKs) and S1P receptors (S1PRs) in tumor growth and acquisition of resistance to chemotherapy in four subtypes of breast cancer that are categorized based on the status of hormone receptors and human epidermal growth factor 2 (HER2) receptors.

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Cell migration activated by platelet‐derived growth factor receptor is blocked by an inverse agonist of the sphingosine 1‐phosphate receptor‐1

Cited by 76 publications

References 32 publications

Insulin-like Growth Factors Mediate Heterotrimeric G Protein-dependent ERK1/2 Activation by Transactivating Sphingosine 1-Phosphate Receptors

Insulin-like Growth Factors Mediate Heterotrimeric G Protein-dependent ERK1/2 Activation by Transactivating Sphingosine 1-Phosphate Receptors

Thematic Review Series: Sphingolipids. Cross-talk at the crossroads of sphingosine-1-phosphate, growth factors, and cytokine signaling*

Involvement of Sphingosine Kinases/Sphingosine-1-Phosphate (S1P)/S1P Receptors in Breast Cancer Subtypes

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