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First published online October 11, 2005
doi: 10.1242/10.1242/jcs.02637

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Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling

¹ Department of Biochemistry, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, VA 23298, USA
² Research and Development, Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, VA 23249, USA

View larger version (17K): [in a new window]   Fig. 1. Bioactive sphingolipid metabolites. The schematic depicts the sphingolipid biosynthetic pathway: LPP, lipid phosphate phosphatase; SPP-1, S1P phosphatase-1; CERK, ceramide kinase; SphK, sphingosine kinase; SM, sphingomyelin. Differential/opposing signaling roles of sphingosine, S1P, ceramide and C1P are indicated. Because of the interconvertibility of these molecules, the activity of a single enzyme in the depicted pathways may affect the fate of the cell.

View larger version (32K): [in a new window]   Fig. 2. Roles of SphK1 and CERK in eicosanoid synthesis. The roles of S1P and C1P in eicosanoid synthesis in response to inflammatory cytokines are indicated, beginning with the first step, induction of cyclooxygenase-2 (COX-2). This `primes' the cell for PGE2 synthesis and requires the generation of S1P by SphK1, followed by a receptor-mediated signaling event initiated by interaction of S1P with its receptor. The second step of prostanoid biosynthesis in response to IL-1ß, involves the activation of cPLA2 and generation of arachidonic acid (AA), which requires CERK and the generation of C1P.

View larger version (32K): [in a new window]   Fig. 3. SphK1 and CERK in mast cell functions. Crosslinking of the high affinity IgE receptor FcRI on mast cells translocates and activates SphK1, increasing S1P formation. S1P in turn transactivates S1P1 and S1P2 receptors, leading to mast cell degranulation and cell motility. Furthermore, CERK may also regulate degranulation of mast cells.

View larger version (20K): [in a new window]   Fig. 4. (A) SphK and S1P signaling in responses of A. thaliana guard cells to abscisic acid (ABA). ABA stimulates SphK and formation of S1P and/or phyto-S1P. Phosphorylated sphingoid bases, acting through the heterotrimeric G protein GPA1 by a mechanism that is still not known, inhibit inwardly rectifying K+ channels and activate slow anion channels, thereby inhibiting stomatal opening and promoting stomatal closure. S1P and/or phyto-S1P can also stimulate cell proliferation in a GPA1-dependent manner. (B) Structures of phytosphingosine, dihydrosphingosine, and sphingosine.

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