Sphingosine-1-phosphate: an enigmatic signalling lipid
The evolutionarily conserved actions of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), in yeast, plants and mammals have shown that it has important functions. In higher eukaryotes, S1P…
Molecular Cloning and Functional Characterization of a Novel Mammalian Sphingosine Kinase Type 2 Isoform*
Northern blot analysis revealed that SPHK2 mRNA expression had a strikingly different tissue distribution from that of SPHK1 and appeared later in embryonic development, and is another member of a growing class of sphingolipid kinases that may have novel functions.
Regulation of Histone Acetylation in the Nucleus by Sphingosine-1-Phosphate
Him Hait et al. (p. 1254) report that S1P can also function by direct binding to the nuclear enzymes, histone deacetylases (HDACs) 1 and 2, which are direct intracellular targets of S 1P and link nuclear S1p to epigenetic regulation of gene expression.
Sphingosine-1-phosphate signaling and its role in disease.
SPHINGOSINE-1-PHOSPHATE: A MISSING COFACTOR FOR THE E3 UBIQUITIN LIGASE TRAF2
The data show that TRAF2 is a novel intracellular target of S1p, and that S1P is the missing cofactor for TRAF 2 E3 ubiquitin ligase activity, indicating a new paradigm for the regulation of lysine-63-linked polyubiquitination.
Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation.
The data reveal Edg-1 to be the first G protein-coupled receptor required for blood vessel formation and show that sphingolipid signaling is essential during mammalian development.
Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate
It is reported that sphingosine-1-phosphate prevents the appearance of the key features of apoptosis, namely intranucleosomal DNA fragmentation and morphological changes, which result from increased concentrations of ceramide.
The outs and the ins of sphingosine-1-phosphate in immunity
Recent advances in understanding of the roles of S1P receptors are discussed and the newly identified intracellular targets of S 1P that are crucial for immune responses are described.
“Inside-Out” Signaling of Sphingosine-1-Phosphate: Therapeutic Targets
Recent preclinical and clinical trials of therapies targeting S1P signaling, including 2-amino-2-propane-1,3-diol hydrochloride (FTY720, fingolimod), S 1P receptor agonists, sphingosine kinase inhibitors, and anti-S1P monoclonal antibody are described.
Essential Role for Sphingosine Kinases in Neural and Vascular Development
- K. Mizugishi, T. Yamashita, A. Olivera, G. Miller, S. Spiegel, R. Proia
- Biology, ChemistryMolecular and Cellular Biology
- 15 December 2005
It is shown that S1P signaling is critical for neural and vascular development and joins a growing list of signaling molecules, such as vascular endothelial growth factor, which regulate the functionally intertwined pathways of angiogenesis and neurogenesis.