Extracellular actions of sphingosine I-phosphate through endothelial differentiation gene products in mammalian cells: role in regulating proliferation and apoptosis
Sphingosine 1-phosphate (SIP) belongs to a group of platelet-derived lipid mediators that regulate cell differentiation, survival and proliferation. It is released from platelets after their activation with agents such as thrombin [l]. In addition, intracellular levels of S1 P are increased in several cell types in response to stimulation by a variety of agonists that include platelet-derived growth factor (PDGF) [2,3], tumour necrosis factor 01 (TNFa), nerve growth factor (NGF), vitamin D,, carbachol (acting at M2 and M3 muscarinic acetylcholine receptors), protein kinases C activators (such as phorbol esters), CAMP elevating agents and the cross-linking of antigen to FcRl or FcyRl receptors. SIP is formed by the phosphorylation of sphingosine, which is catalysed by sphingosine kinase [4]