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Sphingosine‐1‐Phosphate in Cell Growth and Cell Death a
Author(s) -
SPIEGEL SARAH,
CUVILLIER OLIVIER,
EDSALL LISA C.,
KOHAMA TAKAFUMI,
MENZELEEV RAMIL,
OLAH ZOLTAN,
OLIVERA ANA,
PIRIANOV GRISHA,
THOMAS DIANNE M.,
TU ZHENXING,
BROCKLYN JAMES R.,
WANG FANG
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb09658.x
Subject(s) - ceramide , sphingolipid , sphingosine kinase , sphingosine , sphingosine 1 phosphate , lipid signaling , microbiology and biotechnology , sphingomyelin , mapk/erk pathway , biology , apoptosis , cell growth , kinase , programmed cell death , second messenger system , signal transduction , biochemistry , receptor , membrane
Recent evidence suggests that branching pathways of sphingolipid metabolism may mediate either apoptotic or mitogenic responses depending on the cell type and the nature of the stimulus. While ceramide has been shown to be an important regulatory component of apoptosis induced by tumor necrosis factor alpha and Fas ligand, sphingosine‐1‐phosphate (SPP), a further metabolite of ceramide, has been implicated as a second messenger in cellular proliferation and survival induced by platelet‐derived growth factor, nerve growth factor, and serum. SPP protects cells from apoptosis resulting from elevations of ceramide. Inflammatory cytokines stimulate sphingomyelinase, but not ceramidase, leading to accumulation of ceramide, whereas growth signals also stimulate ceramidase and sphingosine kinase leading to increased SPP levels. We propose that the dynamic balance between levels of sphingolipid metabolites, ceramide, and SPP, and consequent regulation of different family members of mitogen‐activated protein kinases (JNK versus ERK), is an important factor that determines whether a cell survives or dies.