Table 1.
Signaling pathways mediated by S1PR1-5.
| Pathway | People | Time | Effect | |
|---|---|---|---|---|
| S1PR1 | Inhibit AC through Giα [107] | Okamoto et al. [107] | 1998 | (1) Reduce cyclic adenosine phosphate (cAMP), promote cell proliferation, and increase survival/prevent cell apoptosis (2) Increase intracellular free calcium and promote insulin secretion at high glucose levels [108] (3) Promote erythrocyte migration, enhance endothelial barrier function and induce vasodilation, and reduce the occurrence of diabetic macrovascular complications [109] |
| Activate PLC via Giβγ, Ras-MAPK [107], PI3K/Akt [110] | Lee et al. [110] | 1999 | ||
| S1PR2 | Activate PI3K through Giβγ, Ras | Kon et al. [111] | 1997 | (1) Promote cell proliferation, increase survival/prevent cell apoptosis, and increase intracellular free calcium (2) Inhibit migration, reduce endothelial barrier function, and induce vasoconstriction (3) Increase cyclic adenosine phosphate (cAMP) (4) Mediate the occurrence of diabetic retinopathy [112] |
| Activate PLC via Gq | ||||
| Activate Rho via G13 | ||||
| Activate AC [111], JNK, and p38 [23] | Gonda et al. [23] | 1999 | ||
| S1PR3 | Inhibit AC through Giα | Okamoto et al. [113] | 1999 | (1) Reduce cAMP (2) Increase intracellular free calcium, promote cell proliferation, and promote insulin secretion at high glucose levels [108] (3) Reduce cytokine-induced islet β cell apoptosis [32, 114] (4) Promote endothelial cell migration and induce vasodilation (5) Mediate local inflammation of the kidney in diabetic nephropathy [17] |
| Activate PLC, PI3K, and Ras via Giβγ | ||||
| Activate PLC via Gq | ||||
| Activate Rho via G13 [113] | ||||
| Activate AC [115] | Malek et al. [115] | 2001 | ||
| S1PR4 | Activation of Cdc 42 through Giβγ [116] | Kohno et al. [116] | 2003 | (1) Mainly expressed in lymphoid tissue, lungs, the brain (especially oligodendrocytes), white blood cells, and the spleen [117]. The role is not clear. |
| PLC [118] | Yamazaki et al. [118] | 2000 | ||
| ERK [119] | Van Brocklyn et al. [119] | 2000 | ||
| Activate Rho via G12/13 [38] | Graler et al. [120] | 2003 | ||
| S1PR5 | Inhibit AC through Giα [121] | Im et al. [121] | 2000 | (1) Mainly expressed in lymphoid tissue, lungs, the brain (especially oligodendrocytes), white blood cells, and the spleen [117]. The role is not clear. |
| Inhibit ERK, activate JNK, couple G12 [115] | Malek et al. [115] | 2001 |