S1PR1
Function
G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis (By similarity). Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury.
Post-translational modifications
S1P-induced endothelial cell migration requires the PKB/AKT1-mediated phosphorylation of the third intracellular loop at the Thr-236 residue.
Palmitoylated by ZDHHC5. Palmitoylation is required for targeting to plasma membrane, enabling G(i) coupling.
Sequence Similarities
Belongs to the G-protein coupled receptor 1 family.
Tissue Specificity
Endothelial cells, and to a lesser extent, in vascular smooth muscle cells, fibroblasts, melanocytes, and cells of epithelioid origin.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Endosome
- Membrane raft
- Recruited to caveolin-enriched plasma membrane microdomains in response to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine. Ligand binding leads to receptor internalization.
Alternative names
CD363, CHEDG1, EDG1, S1PR1, Sphingosine 1-phosphate receptor 1, S1P receptor 1, S1P1, Endothelial differentiation G-protein coupled receptor 1, Sphingosine 1-phosphate receptor Edg-1, S1P receptor Edg-1