Roles of sphingosine-1-phosphate signaling in angiogenesis

Figure 1 Receptor-subtype-specific signaling mechanisms of S1P₁, S1P₂ and S1P₃. These three receptors activate partially overlapping but distinct sets of signaling pathways via coupling to different sets of the heterotrimeric G proteins. S1P₁ and S1P₃ induce activation of Rac in a G_i-dependent manner to stimulate cell migration, whereas S1P₂ inhibits Rac via G_12/13-Rho to mediate inhibition of cell migration. S1P₂ also stimulates 3’-specific polyphosphoinositide phosphatase “phosphatase and tensin homolog deleted from chromosome 10” (PTEN) to inhibit the serine/threonine protein kinase Akt, which probably participates in inhibition of cell migration. S1P: Sphingosine-1-phosphate.