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Titolo:
Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival
Autore:
Olivera, A; Kohama, T; Edsall, L; Nava, V; Cuvillier, O; Poulton, S; Spiegel, S;
Indirizzi:
Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 ol Biol, Washington, DC 20007 USA
Titolo Testata:
JOURNAL OF CELL BIOLOGY
fascicolo: 3, volume: 147, anno: 1999,
pagine: 545 - 557
SICI:
0021-9525(19991101)147:3<545:SKEIIS>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
SIGNAL-TRANSDUCTION PATHWAYS; PROTEIN-COUPLED RECEPTORS; SWISS 3T3 FIBROBLASTS; SACCHAROMYCES-CEREVISIAE; SURFACE-RECEPTOR; SPHINGOLIPID METABOLISM; LYSOPHOSPHATIDIC ACID; CALCIUM MOBILIZATION; EXTRACELLULAR ACTION; NEURITE RETRACTION;
Keywords:
sphingosine kinase; sphingosine-1-phosphate; cell growth; apoptosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
80
Recensione:
Indirizzi per estratti:
Indirizzo: Spiegel, S Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, 3900 Reservoir Rd NW, Washington, DC 20007 USA Georgetown Univ 3900 Reservoir Rd NW Washington DC USA 20007 SA
Citazione:
A. Olivera et al., "Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival", J CELL BIOL, 147(3), 1999, pp. 545-557

Abstract

Sphingosine-1-phosphate (SPP) is a bioactive lipid that has recently been identified as the ligand for the EDG family of G protein-coupled cell surface receptors. However, the mitogenic and survival effects of exogenous SPP may not correlate with binding to cell-surface receptors (Van Brocklyn, J.R., M.J. Lee, R. Menzeleev; A. Olivera, L. Edsall, O. Cuvillier, D.M. Thomas, P.J.P. Coopman, S, Thangada, T. Hla, and S. Spiegel. 1998. J. Cell Biol. 142:229-240). The recent cloning of sphingosine kinase. a unique lipid kinase responsible for the formation of SPP, has provided a new tool to investigate the role of intracellular SPP. Expression of sphingosine kinase markedly increased SPP levels in NIH 3T3 fibroblasts and HEK293 cells, but no detectable secretion of SPP into the medium was observed. The increased sphingosine kinase activity in NIH 3T3 fibroblasts was sufficient to promote growth in low-serum media, expedite the G(1)/S transition, and increase DNA synthesis and the proportion of cells in the S phase of the cell cycle with a concomitant increase in cell numbers. Transient or stable overexpression ofsphingosine kinase in NIH 3T3 fibroblasts or HEK293 cells protected against apoptosis induced by serum deprivation or ceramide elevation. N,N-Dimethylsphingosine, a competitive inhibitor of sphingosine kinase, blocked the effects of sphingosine kinase overexpression on cell proliferation and suppression of apoptosis, In contrast, pertussis toxin did not abrogate these biological responses. In Jurkat T cells, overexpression of sphingosine kinase also suppressed serum deprivation- and ceramide-induced apoptosis and, to alesser extent, Fas-induced apoptosis, which correlated with inhibition of DEVDase activity, as well as inhibition of the executionary caspase-3. Taken together with ample evidence showing that growth and survival factors activate sphingosine kinase, our results indicate that SPP functions as a second messenger important for growth and survival of cells. Hence, SPP belongsto a novel class of lipid mediators that can function inside and outside cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 04:09:10