Figure 1. Biosynthesis and transport of S1P. SPHKs phospholylate sphingosine (Sph) to S1P. S1P is secreted into the extracellular space via the S1P transporter. Chaperone proteins (i.e., Apolipoprotein M [ApoM] and Albumin) enable S1P transport. Extracellular S1P binds to S1PRs on cell membranes via autocrine or paracrine mechanisms. S1P binding to S1PRs initiates cellular responses via G-proteins, influencing cell proliferation, migration, contraction, and survival. Graphical objects were created with BioRender (https://biorender.com/).
Cer: ceramide; HDL: high-density lipoprotein; Hex: hexadecenal; PE: phosphoethanolamine; SIP: sphingosine-1-phosphate; SIPR: sphingosine-1-phosphate receptor; SPHK: Sphingosine kinase.
From: Sphingolipid Signaling in Vascular Smooth Muscle Cells during Development and Diseases
Figure 2. S1P receptors (S1PRs) and downstream signaling. S1PRs are G protein-coupled receptors. The binding of S1P to S1PRs leads to the activation of G-proteins (Gi/o, Gq, G12/13). G-proteins regulate the activation or inhibition of the downstream signaling pathways. Graphical objects were created with BioRender (https://biorender.com/).
AC: adenylyl cyclase; Camp: cyclic adenosine monophosphate; ERK: extracellular signal-regulated kinases; PI3K: phosphatidylinositol-3 kinase; PLC: phospholipase C; SIP: sphingosine-1-phosphate.
From: Sphingolipid Signaling in Vascular Smooth Muscle Cells during Development and Diseases
Figure 3. Sphingolipid signaling regulates vascular disease and homeostasis. Examples of the influences of S1P-S1PRs signaling on vascular diseases and homeostasis. Even the same receptors can have different effects depending on the type of disease, vascular bed, or cell type. Graphical objects were created with BioRender (https://biorender.com/).
EC: endothelial cell; S1P: sphingosine-1-phosphate; S1PR: S1P receptor; VSMC: vascular smooth muscle cell.
From: Sphingolipid Signaling in Vascular Smooth Muscle Cells during Development and Diseases
