Sphingosine 1-phosphate receptor 1

Definition:

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.

References:

[1]. Michael A Hanson, et al. Crystal structure of a lipid G protein-coupled receptor. Science. 2012 Feb 17;335(6070):851-5. [Content Brief]

[2]. M J Lee, et al. Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science. 1998 Mar 6;279(5356):1552-5. [Content Brief]

[3]. J P Hobson, et al. Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science. 2001 Mar 2;291(5509):1800-3. [Content Brief]

[4]. A L Parrill, et al. Identification of Edg1 receptor residues that recognize sphingosine 1-phosphate. J Biol Chem. 2000 Dec 15;275(50):39379-84. [Content Brief]

[5]. M J Lee, et al. Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Mol Cell. 2001 Sep;8(3):693-704. [Content Brief]

[6]. M J Lee, et al. The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway. J Biol Chem. 1996 May 10;271(19):11272-9. [Content Brief]

[7]. D A Wang, et al. A single amino acid determines lysophospholipid specificity of the S1P1 (EDG1) and LPA1 (EDG2) phospholipid growth factor receptors. J Biol Chem. 2001 Dec 28;276(52):49213-20. [Content Brief]

[8]. Patrick A Singleton, et al. Akt-mediated transactivation of the S1P1 receptor in caveolin-enriched microdomains regulates endothelial barrier enhancement by oxidized phospholipids. Circ Res. 2009 Apr 24;104(8):978-86. [Content Brief]

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