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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs.

Strathprints serves world leading Open Access research by the University of Strathclyde, including research by the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), where research centres such as the Industrial Biotechnology Innovation Centre (IBioIC), the Cancer Research UK Formulation Unit, SeaBioTech and the Centre for Biophotonics are based.

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Sphingosine 1-phosphate regulation of extracellular signal regulated kinase-1/2 in embyronic stem cells

Rodgers, A. and Mormeneo, D. and Long, J.S. and Delgado, A. and Pyne, N.J. and Pyne, S. (2009) Sphingosine 1-phosphate regulation of extracellular signal regulated kinase-1/2 in embyronic stem cells. Stem Cells and Development, 18 (9). pp. 1319-1330. ISSN 1547-3287

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Abstract

Recent evidence suggests that sphingosine 1-phosphate (S1P) regulates self-renewal of human embryonic stem (ES) cells and differentiation of mouse embryoid bodies (derived from mouse ES cells) to cardiomyocytes. We have investigated the role of S1P in regulating ERK-1/2 signaling in mouse ES cells. In this regard, we found that both mouse ES-D3 and CGR8 cells express S1P1, S1P2, S1P3, and S1P5 but lack S1P4. The treatment of ES cells with S1P induced the activation of ERK-1/2 via a mechanism that was not mediated by S1P1, S1P2, or S1P3. This was based on: (i) the failure of S1P1, S1P2, or S1P3 antagonists to inhibit S1P-stimulated ERK-1/2 activation and (ii) the failure of SEW 2871 (S1P1 receptor agonist) to stimulate ERK-1/2 activation. The treatment of ES cells with phytosphingosine 1-phosphate (phyto-S1P), which we show here is an agonist of the S1P5 receptor, stimulated ERK-1/2 activation. These findings therefore suggest that S1P5 may mediate the effects of S1P in terms of regulating ERK-1/2 signaling in ES cells. The S1P-dependent activation of ERK-1/2 was sensitive to inhibition by pertussis toxin (uncouples the G-protein, Gi from GPCR), bisindolylmaleimide I (PKC inhibitor), and PP2 (c-Src inhibitor), but was not reduced by LY29004 (PI3K inhibitor) suggesting that S1P uses Gi-, PKC-, and c-Src-dependent mechanisms to activate the ERK-1/2 pathway in ES cells.