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Details for receptor: Sphingosine 1-phosphate receptor 1

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EndoNet ID: ENR00755

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Synonyms

  • edg1
  • S1PR1
  • Sphingosine 1-phosphate receptor Edg-1
  • Endothelial differentiation G-protein coupled receptor 1
  • Sphingosine 1-phosphate receptor 1

General information

  • Belongs to the G-protein coupled receptor 1 family.
  • Seems to be coupled to the G(i) subclass of heteromeric G proteins.

Links to other resources

UniProt P21453
Ensembl ENST00000424264

Subunit information

Subunit (1 times)

Sequence 
MGPTSVPLV KAHRSSVSD YVNYDIIVR 
HYNYTGKLN ISADKENSI KLTSVVFIL 
ICCFIILEN IFVLLTIWK TKKFHRPMY 
YFIGNLALS DLLAGVAYT ANLLLSGAT 
TYKLTPAQW FLREGSMFV ALSASVFSL 
LAIAIERYI TMLKMKLHN GSNNFRLFL 
LISACWVIS LILGGLPIM GWNCISALS 
SCSTVLPLY HKHYILFCT TVFTLLLLS 
IVILYCRIY SLVRTRSRR LTFRKNISK 
ASRSSEKSL ALLKTVIIV LSVFIACWA 
PLFILLLLD VGCKVKTCD ILFRAEYFL 
VLAVLNSGT NPIIYTLTN KEMRRAFIR 
IMSCCKCPS GDSAGKFKR PIIAGMEFS 
RSKSDNSSH PQKDEGDNP ETIMSSGNV 
NSSS
UniProt P21453-1

Binding hormones

  • sphingosine 1-phosphate
    • Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P).
  • Sphingosylphosphorylcholine
    • All of the subsequently identified S1P receptors of the EDG family exhibited a low affinity for SPC and might thus rather mediate some of SPC's extracellular actions in the low micromolar concentration range. [1]

Anatomical structures with this receptor

  • continuous_vascular_endothelial_cell_of_blood_vessels_and_lymphatics

    Induced phenotypes

    • cell-cell junction organization
      • S1PR1 has an important role in strengthening endothelial-cell–endothelial-cell junctional contacts. [2]
    • vasculogenesis
      • S1PR1 has an important role in regulating endothelial-cell organization during development. [3]
    • positive regulation of endothelial cell migration
      • S1P stimulates the migration of endothelial cells. [4]
    • regulation of endothelial cell differentiation
      • S1PR1 is the receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. This inducible epithelial cell G-protein-coupled receptor may be involved in the processes that regulate the differentiation of endothelial cells. [5]

  • smooth_muscle_cell

    Induced phenotypes

    • positive regulation of smooth muscle cell migration
      • Overexpression of S1PR1 in VSMCs enhances migration response to S1P. [6]
    • heart development
      • Direct evidence for S1P receptor signaling in angiogenesis and cardiovascular development comes from the phenotype of genetic-null studies in mice. The s1p1-null embryos die in utero because of defective vascular maturation in which VSMCs/pericytes do not migrate to surround the vessels. [7]
    • positive regulation of angiogenesis
      • S1P receptor edg-1 is essential for cardiovascular development. [7]
      • Edg-1 is the first G protein-coupled receptor required for blood vessel formation. In general, sphingolipid signaling is essential during mammalian development. [7]
    • regulation of inflammatory response
      • In vascular smooth muscle cells, S1P stimulates DNA synthesis in association with ERK activation, and may play a central role in excessive fibroproliferative and inflammatory response to vascular injury that are hallmarks of atherosclerois progression. [8]
      • a central role for S1P1 in vascular smooth muscle cell migration was established by the phenotype of S1P1-deficient mice in which those cells do not migrate properly to surround and reinforce nascent vessels. [9]

  • fibroblast

  • epithelial_cell

  • melanocyte

  • immune_system

    Induced phenotypes

    • positive regulation of chemotaxis
      • The effect of S1P on S1PR1-mediated chemotaxis can depend on S1P concentration in vitro; low concentrations of S1P promote chemotaxis. [10]
    • negative regulation of chemotaxis
      • The effect of S1P on S1PR1-mediated chemotaxis can depend on S1P concentration in vitro; high concentrations of S1P seem to be inhibitory. This inhibitory effect might partly be due to the downregulation of S1PR1 by high concentrations of S1P. [11]
    • regulation of leukocyte migration
      • S1PR1 controls the exit of haematopoietic stem and progenitor cells (HSPCs) from non-lymphoid peripheral tissues to the draining lymphatics. [12]
    • regulation of leukocyte migration
      • S1P signalling has a role in both the homing of immune cells to lymphoid organs, and in controlling their egress into blood and lymph. [13]
      • S1PR1 is decisive for the exit of mature thymocytes — both conventional T cells and natural killer T (NKT) cells — from the thymus. [14]

  • dendritic_cell_in_lymphoid_tissues

    Induced phenotypes

    • dendritic cell chemotaxis
      • FTY720, a S1P receptor agonist, can severly hamper migration of dendritic cells to the lymph nodes suggesting additional mechanisms underlying the immunosuppressive effects of this spingosine analog. [15]

  • eosinophil_granulocyte

  • macrophage

    Induced phenotypes

    • negative regulation of cytokine production
      • Peritoneal macrophages from low-density lipoprotein-receptor-deficient mice, which are a model for atherosclerosis, that had been treated with FTY720 (FTY720 is a sphingosine analogue that could be phosphorylated by SPHKs to produce a S1PR ligand with potent effects, including S1PR agonism and the downregulation of S1PR expression) had a markedly decreased production of inflammatory tumour-necrosis factor (TNF), TNF receptor (TNFR) and IL-6 in response to LPS. [16]

  • mast_cell

    Induced phenotypes

    • positive regulation of mast cell chemotaxis
      • Loss of S1PR1 results in decreased chemotactic motility. [17]
      • The positive effect of S1PR1 on mast-cell chemotactic motility is counteracted by S1PR2 expression. [17]

  • T-lymphocyte

    Induced phenotypes

    • cell maturation
      • Upregulation of S1PR1 expression or increased S1PR1 signalling suppresses the proliferation and maturation of mouse T cells. [18]
    • negative regulation of interferon-gamma production
      • In CD4+T cells, signalling through S1PR1 inhibits IFNgamma production, when compared with IL-4 production. [18]
    • positive regulation of interleukin-4 production
      • In CD4+T cells, signalling through S1PR1 increases IL-4 production. [19]
    • regulation of T cell proliferation
      • S1PR1 might modulate the proliferation of T cells. [20]
    • T cell differentiation during immune response
      • S1PR1 might decrease TH1-cell responses in vivo. [20]
      • S1PR1 might increase TH2-cell responses. [20]
      • S1PR1 might polarize TCR-activated cells towards a T helper 17-cell phenotype, thereby altering the immune response. [20]
      • S1P seems to increase the size of the TH17-cell subset through S1PR1 triggering. [21]
    • positive regulation of leukocyte migration
      • S1P has been reported to stimulate migration of T cells that express s1p1 under some conditions. T cell receptor-mediated activation of T cells suppresses expression of s1p1, and it has been reported to eliminate their migration responses to S1P. [22]
    • regulation of leukocyte migration
      • S1P signalling has a role in both the homing of immune cells to lymphoid organs, and in controlling their egress into blood and lymph. [13]
      • S1PR1 is decisive for T-cell egress from lymph nodes. [14]

  • B-lymphocyte

    Induced phenotypes

    • regulation of leukocyte migration
      • During an antibody response, S1PR1 on IgG-secreting plasma cells is required for the cells to move from the spleen into the blood and, ultimately, to the bone marrow. [23]
      • A similar scenario seems to exist for IgA-producing B cells, which require S1P signalling to migrate out of Peyers patches. [24]
      • In addition to homing to and egress from lymphoid tissues, S1P signalling functions to properly compartmentalize immune cells in lymphoid tissues. An example is the localization and movement of marginal-zone B cells in the spleen, which depend on their expression of S1PR1. [25]
      • S1P signalling has a role in both the homing of immune cells to lymphoid organs, and in controlling their egress into blood and lymph. [13]
      • S1PR1 is decisive for B- cell egress from lymph nodes. [10]

  • killer_T_cell

    Induced phenotypes

    • positive regulation of chemotaxis
      • S1P induces chemotaxis of thymocytes, T and B lymphocytes. [8]

  • leukocyte

  • lymphocyte

    Induced phenotypes

    • regulation of lymphocyte proliferation
      • The downregulation of S1PR1 expression that occurs after TCR activation seems to contribute to the retention and proliferation of antigen-bearing cells in the lymph nodes. [10]
    • regulation of leukocyte migration
      • Lymphocytes that lack S1PR1 expression cannot egress from lymph nodes and thymus, and lymphocytes with decreased receptor expression levels have a corresponding decreased rate of egress. [10]

  • osteoblast

  • vascularendothelial_cell

    Induced phenotypes

    • regulation of cardiovascular system
      • S1P was also shown to regulate the cardiovascular system; intravenous administration of S1P decreased heart rates, ventricular contraction, and blood pressure in rats. [26]
    • positive regulation of blood vessel endothelial cell migration
      • S1P induces migration of VECs. [27]
      • S1P receptor-mediated signaling plays a major regulatory role in angiogenesis. [28]
      • VEC migration is inhibited by antisense oligonucleotides against s1p1. [29]
    • positive regulation of endothelial cell proliferation
      • S1P induces proliferation of VECs. [30]
      • S1P receptor-mediated signaling plays a major regulatory role in angiogenesis. [28]
    • positive regulation of angiogenesis
      • S1P1 plays a primary role in angiogenesis by its potent activation of Rac, potentially through the intimate interplay with PDGF. [27]
    • adherens junction assembly
      • S1P-induced VEC adherens junction assembly and cell barrier integrity are blocked by antisense oligonucleotides against s1p1. [31]
      • Expression of a dominant negative S1P1 mutant inhibits S1P-induced VEC assembly and migration. [27]
      • S1P stimulates the formation and maintenance of VECs assembly/integrity by activating S1P1. [32]

  • umbilical_vein_endothelial_cells

    Induced phenotypes

    • venous endothelial cell differentiation
      • EDG1 was identied as an immediate-early gene product in phorbol ester-differentiated human umbilical vein endothelial cells, and was suggested to play a role in the morphogenetic differentiation of vascular endothelial cells into capillary-like tubules and in angiogenesis. [33]

  • spleen

  • brain

    Induced phenotypes

    • positive regulation of neurogenesis
      • Embryos lacking S1P exhibit severely disturbed neurogenesis, including neural tube closure, and angiogenesis. [8]
      • S1P1 receptor-null mice also showed severe defects in neurogenesis. [34]

  • heart

  • lung

    Influences

    • positive interleukin 6
      • SP1 stimulates IL-6 prodcution in airway smooth muscle cells. [35]

  • adipose_tissue

  • liver

    Induced phenotypes

    • hepatic stellate cell migration
      • S1P1 regulates migration and fibrogenic activation of HSCs. [36]

  • thymus

  • kidney

  • skeleton_muscle

  • keratinocyte

Reference