Figure 3. S1P signaling in the nucleus.
Recently, nuclear functions of S1P have been revealed. Signaling through nuclear-associated S1P1 regulates gene transcription in endothelial cells and T-cells, thereby affecting vasculature and immune functions 59,60. S1P formed by SphK2 inhibits histone deacetylases. Complexes containing SphK2 and histone deacetylases are enriched in the promotor regions of p21 and c-fos genes 18. S1P5 and both SphK isoforms are found within the centrosome, where they have been postulated to play a role in spindle formation and mitosis 15.