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Verzijl, Dennis,Peters, Stephan L.M.,Alewijnse, Astrid E. Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.29 No.2
Regulatory processes including receptor phosphorylation and intracellular trafficking, also referred to as receptor internalization, are important processes to terminate G protein-coupled receptor (GPCR) signaling. Compelling evidence now indicates that internalization of a receptor is not necessarily the endpoint of signaling, but can also be the beginning of the activation of intracellular signaling pathways. Sphingosine-1-phosphate (S1P) receptors, which are activated by the endogenous phospholipid S1P, belong to the family of GPCRs. Interestingly, there is evidence indicating differential intracellular trafficking of one of the S1P receptor subtypes, the S1P1 receptor, upon agonist activation by either S1P or the synthetic agonist FTY720-P. Moreover, the differential effect of FTY720-P on $S1P_1$ receptor regulation has been suggested to be the mechanism of action of this drug, which is now in Phase III clinical trials for the treatment of multiple sclerosis. It is thus of importance to get a good insight into the regulation of S1P receptors. This review therefore gives a detailed overview about the current state of knowledge on S1P receptor internalization and its functional implications, including some data on nuclear signaling of S1P receptors.
Dennis Verzijl,Stephan L.M. Peters,Astrid E. Alewijnse 한국분자세포생물학회 2010 Molecules and cells Vol.29 No.2
Regulatory processes including receptor phosphorylation and intracellular trafficking, also referred to as receptor internalization, are important processes to terminate G protein-coupled receptor (GPCR) signaling. Compelling evidence now indicates that internalization of a receptor is not necessarily the endpoint of signaling, but can also be the beginning of the activation of intracellular signaling pathways. Sphingosine-1-phosphate (S1P) receptors, which are ac-tivated by the endogenous phospholipid S1P, belong to the family of GPCRs. Interestingly, there is evidence indi-cating differential intracellular trafficking of one of the S1P receptor subtypes, the S1P1 receptor, upon agonist activa-tion by either S1P or the synthetic agonist FTY720-P. Moreover, the differential effect of FTY720-P on S1P1 re-ceptor regulation has been suggested to be the mecha-nism of action of this drug, which is now in Phase III clini-cal trials for the treatment of multiple sclerosis. It is thus of importance to get a good insight into the regulation of S1P receptors. This review therefore gives a detailed overview about the current state of knowledge on S1P receptor in-ternalization and its functional implications, including some data on nuclear signaling of S1P receptors.
Spijkers, Leon J.A.,Alewijnse, Astrid E.,Peters, Stephan L.M. Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.29 No.2
Vasomotor tone is regulated by a complex interplay of a variety of extrinsic neurohumoral and intrinsic factors. It is the endothelium that has a major influence on smooth muscle cell tone via the release of intrinsic vasoactive factors and is therefore an important regulator of vasomotor tone. Sphingolipids are an emerging class of lipid mediators with important physiological properties. In the last two decades it has not only become increasingly clear that sphingolipid signaling plays a pivotal role in immune function, but also its role in the vascular system is now becoming more recognized. In this mini-review we will highlight the possible cross-talk between sphingolipids and intrinsic vasoactive factors released by the endothelium. Via this cross-talk sphingolipids can orchestrate vasomotor tone and may therefore also be involved in the pathophysiology of disease states associated with endothelial dysfunction.