Sphingosine‐1‐phosphate inhibits actin nucleation and pseudopodium formation to control cell motility of mouse melanoma cells

Yamamura, Soichiro; Sadahira, Yoshito; Ruan, Fuqiang; Hakomori, Sen‐itiroh; Igarashi, Yasuyuki

doi:10.1016/0014-5793(96)00175-5

Cited by 27 publications

(20 citation statements)

References 31 publications

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“…It is possible that H218 is partially activated in the absence of ligand when the receptor is overexpressed, a phenomenon commonly observed for G protein-coupled receptors (47). Our results indicate that H218 may be the unidentified cell surface receptor that was previously suggested in several studies to be responsible for SPP-induced cell morphology alterations and remodeling of the actin cytoskeleton (48,49).…”

Section: Discussionsupporting

confidence: 52%

Sphingosine 1-Phosphate-induced Cell Rounding and Neurite Retraction Are Mediated by the G Protein-coupled Receptor H218

Brocklyn

Edsall

et al. 1999

Journal of Biological Chemistry

177

144

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Sphingosine 1-phosphate (SPP) is a lipid second messenger that also acts as a first messenger through the G protein-coupled receptor Edg-1. Here we show that SPP also binds to the related receptors H218 and Edg-3 with high affinity and specificity. SPP and sphinganine 1-phosphate bind to these receptors, whereas neither sphingosylphosphorylcholine nor lysophosphatidic acid compete with SPP for binding to either receptor. Transfection of HEK293 cells with H218 or edg-3, but not edg-1, induces rounded cell morphology in the presence of serum, which contains high levels of SPP. SPP treatment of cells overexpressing H218 cultured in delipidated serum causes cell rounding. A similar but less dramatic effect was observed in cells overexpressing Edg-3 but not with Edg-1. Cell rounding was correlated with apoptotic cell death, probably as a result of loss of attachment. Nerve growth factor-induced neuritogenesis in PC12 cells was inhibited by overexpression of H218 and to a lesser extent Edg-3. SPP treatment rapidly enhanced neurite retraction in PC12 cells overexpressing Edg-1, Edg-3, or H218. Thus, H218, and possibly Edg-3, may be the cell surface receptors responsible for cell rounding and neurite retraction induced by SPP. Moreover, the identification of these two additional SPP receptors indicates that a family of highly specific receptors exists that mediate different responses to SPP.The sphingolipid metabolite sphingosine 1-phosphate (SPP) 1 is emerging as a member of a new class of lipid second messengers (1, 2). SPP is mitogenic in diverse cell types (3-6) and suppresses programmed cell death or apoptosis (7-10). Various stimuli, including platelet-derived growth factor and serum (6, 11), nerve growth factor (NGF) (8, 12), vitamin D 3 (13), activation of protein kinase C (14, 15) or protein kinase A (10), cross-linking of the Fc⑀R1 (16) or Fc␥R1 (17) receptor by antigens, and binding of carbachol to m2 and m3 muscarinic acetylcholine receptors (18), increase cellular levels of SPP by activation of sphingosine kinase. Moreover, competitive inhibitors of sphingosine kinase eliminate the formation of SPP and selectively block cellular proliferation induced by platelet-derived growth factor and serum (11,19), the cytoprotective effects of protein kinase C and cAMP activators (7, 10), NGF (8), and vitamin D 3 (13) as well as Fc⑀R1-, Fc␥R1-, and muscarinic acetylcholine receptor-mediated calcium signaling (16, 17), further supporting a role for endogenous SPP in cell growth, survival, and calcium mobilization. In addition, microinjected SPP mobilizes calcium from internal sources (18) and is mitogenic for Swiss 3T3 fibroblasts (20), indicating that SPP acts intracellularly to regulate calcium homeostasis and proliferation.Several other responses to SPP are mediated through cell surface receptors, including platelet activation (21), inhibition of melanoma cell motility (22), activation of G i protein-gated inward rectifying K ϩ channels in atrial myocytes (23), and Rho-dependent neurite retraction and cell rounding o...

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Section: Discussionsupporting

confidence: 52%

Sphingosine 1-Phosphate-induced Cell Rounding and Neurite Retraction Are Mediated by the G Protein-coupled Receptor H218

Brocklyn

Edsall

et al. 1999

Journal of Biological Chemistry

177

144

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“…The sphingolipid metabolite, sphingosine-1-phosphate (SPP), which, similar to LPA, can be released from thrombin-activated platelets , has been reported to effectively and specifically inhibit chemotactic motility and invasiveness as well as extracellular matrix protein-induced haptotactic motility of several tumor cell lines (Sadahira et al 1992(Sadahira et al , 1994Yamamura et al 1996). A similar observation was made for platelet-derived growth factor-stimulated migration and chemotaxis of human arterial smooth muscle cells (Bornfeldt et al 1995).…”

Section: Introductionsupporting

confidence: 50%

Sphingolipid receptor signaling and function in human bladder carcinoma cells: inhibition of LPA- but enhancement of thrombin-stimulated cell motility

Rümenapp

Lümmen

Virchow

et al. 2000

Naunyn-Schmiedeberg's Arch Pharmacol

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Sphingosine-1-phosphate (SPP) induces a variety of cellular responses, including Ca2+ signaling, proliferation, and inhibition of motility, apparently by acting at specific G protein coupled receptors. Here, the expression, signaling, and motile responses of sphingolipid receptors were examined in human bladder carcinoma (J82) cells, for which lysophosphatidic acid (LPA) and thrombin act as potent agonists. SPP potently and rapidly mobilized Ca2+, stimulated phospholipases C and D, and inhibited cAMP accumulation, without affecting growth of J82 cells, which express the recently identified SPP receptors, Edg-1 and Edg-3. The effects of SPP were mimicked by sphingosylphosphorylcholine (SPPC) and strongly attenuated by pertussis toxin (PTX). SPP and SPPC by themselves induced a small, PTX-sensitive motile response. However, stimulation of cell motility by LPA, which by itself was also PTX-sensitive, was blocked by SPP and SPPC. In contrast, motility stimulation by thrombin, which by itself was PTX-insensitive, was strongly augmented by the sphingolipids in a PTX-sensitive manner. The bidirectional regulation of LPA- and thrombin-stimulated motility was not due to selective alterations in the activation of Rho GTPases which control cell motility. In fact, RhoA activation and Rho-dependent actin stress fiber formation induced by LPA and thrombin were mimicked, but not altered by SPP and SPPC. We conclude that J82 cells express sphingolipid receptors, coupled via G proteins to several signaling pathways. Most importantly, these sphingolipid receptors potently regulate thrombin- and LPA-stimulated motility, but in opposite directions, suggesting that migration of these human bladder carcinoma cells is controlled by a complex network of interacting extracellular ligands.

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“…S1P (sphingosine 1-phosphate) is a ligand for several GPCRs, and it suppresses the motility of B16 melanoma cells, BALB/c 3T3 cells, and smooth muscle cells (23,24). S1P inhibits the formation of pseudopodia in B16 melanoma cells, and it activates the formation of focal adhesion, but has no effect on integrindependent adhesion to the extracellular matrix (23,25,26). S1P activates focal adhesion kinase and then Rho through Edg-5 GPCR.…”

Section: Discussionmentioning

confidence: 99%

Metastin Suppresses the Motility and Growth of CHO Cells Transfected with Its Receptor

Hori

Honda

Asada

et al. 2001

Biochemical and Biophysical Research Communications

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Sphingosine‐1‐phosphate inhibits actin nucleation and pseudopodium formation to control cell motility of mouse melanoma cells

Cited by 27 publications

References 31 publications

Sphingosine 1-Phosphate-induced Cell Rounding and Neurite Retraction Are Mediated by the G Protein-coupled Receptor H218

Sphingosine 1-Phosphate-induced Cell Rounding and Neurite Retraction Are Mediated by the G Protein-coupled Receptor H218

Sphingolipid receptor signaling and function in human bladder carcinoma cells: inhibition of LPA- but enhancement of thrombin-stimulated cell motility

Metastin Suppresses the Motility and Growth of CHO Cells Transfected with Its Receptor

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