S1P1 receptor

Target id: 275

Nomenclature: S1P1 receptor

Family: Lysophospholipid (S1P) receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     S1P1 receptor has curated GtoImmuPdb data

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 381 1p21 S1PR1 sphingosine-1-phosphate receptor 1
Mouse 7 382 3 G1 S1pr1 sphingosine-1-phosphate receptor 1
Rat 7 383 2q41 S1pr1 sphingosine-1-phosphate receptor 1
Previous and Unofficial Names
CD363 | EDG1 (Edg1) | endothelial differentiation G protein-coupled receptor 1
Database Links
Specialist databases
GPCRDB s1pr1_human (Hs), s1pr1_mouse (Mm), s1pr1_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the S1P1 receptor in complex with sphingolipid mimic ML056
PDB Id:  3V2Y
Ligand:  W146
Resolution:  2.8Å
Species:  Human
References:  22
Natural/Endogenous Ligands
sphingosine 1-phosphate
sphingosylphosphorylcholine
Comments: Sphingosine 1-phosphate exhibits greater potency than sphingosylphosphorylcholine. LPA is a low potency agonist.
Potency order of endogenous ligands
sphingosine 1-phosphate > dihydrosphingosine 1-phosphate > sphingosylphosphorylcholine  [5,38]

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
sphingosine 1-phosphate Hs Agonist 7.9 – 9.4 pKd 15,30
pKd 7.9 – 9.4 (Kd 1.32x10-8 – 3.9x10-10 M) [15,30]
LPA Hs Agonist 5.6 pKd 31
pKd 5.6 [31]
SEW2871 Hs Agonist 5.5 – 7.7 pKi 46
pKi 5.5 – 7.7 (Ki 2.89x10-6 – 1.8x10-8 M) [46]
amiselimod phosphate Hs Agonist 10.1 pEC50 54
pEC50 10.1 (EC50 7.5x10-11 M) [54]
Description: In an intracellular Ca2+ mobilization assay.
ozanimod Hs Agonist 9.4 – 9.8 pEC50 20,36,51
pEC50 9.8 (EC50 1.6x10-10 M) [20,36,51]
Description: In a cAMP assay.
pEC50 9.4 (EC50 4.1x10-10 M) [51]
Description: In a GTPγS assay.
siponimod Hs Agonist 9.4 pEC50 41
pEC50 9.4 (EC50 4x10-10 M) [41]
Description: In a GTPγS binding assay
ponesimod Hs Agonist 9.1 pEC50 7
pEC50 9.1 (EC50 7.6x10-10 M) [7]
Description: In a radioligand binding assay using membranes from CHO cells expressing human S1P1
KRP 203-phosphate Mm Agonist 9.1 pEC50 52
pEC50 9.1 [52]
AUY954 Mm Agonist 9.1 pEC50 42
pEC50 9.1 (EC50 9x10-10 M) [42]
AUY954 Hs Agonist 8.9 pEC50 42
pEC50 8.9 (EC50 1.2x10-9 M) [42]
CYM5442 Hs Agonist 8.9 pEC50 20
pEC50 8.9 [20]
sphingosine 1-phosphate Mm Agonist 8.9 pEC50 42,46
pEC50 8.9 (EC50 1.4x10-9 M) [42,46]
FTY720-phosphate Mm Agonist 8.2 – 9.5 pEC50 8,52
pEC50 8.2 – 9.5 [8,52]
FTY720-phosphate Hs Agonist 8.1 – 9.5 pEC50 8,17,42,56
pEC50 9.5 (EC50 3x10-10 M) [17,42]
pEC50 8.1 – 9.5 [8,17,42,56]
compound 43 [PMID: 26751273] Hs Agonist 8.8 pEC50 14
pEC50 8.8 [14]
Description: In β-arrestin and receptor internalisation assays.
AFD(R) Hs Agonist 8.4 – 8.8 pEC50 8
pEC50 8.4 – 8.8 [8]
CYM5181 Hs Agonist 8.5 pEC50 20
pEC50 8.5 [20]
sphingosine 1-phosphate Hs Agonist 7.1 – 9.4 pEC50 8,27,38,42,46
pEC50 7.1 – 9.4 (EC50 1x10-9 – 4x10-10 M) [8,27,38,42,46]
etrasimod Hs Agonist 8.2 pEC50 11
pEC50 8.2 (EC50 6.1x10-9 M) [11]
Description: In a β-arrestin recruitment assay.
SEW2871 Hs Agonist 7.5 – 7.9 pEC50 20,46
pEC50 7.5 – 7.9 (EC50 2.88x10-8 – 1.26x10-8 M) [20,46]
SEW2871 Mm Agonist 7.7 pEC50 46
pEC50 7.7 (EC50 2.07x10-8 M) [46]
FTY720-phosphate Hs Agonist 9.5 pIC50 17
pIC50 9.5 (IC50 3x10-10 M) [17]
compound 26 [PMID: 16190743] Hs Agonist 9.2 pIC50 32
pIC50 9.2 [32]
ASP4058 Hs Agonist 8.1 pIC50 57
pIC50 8.1 (IC50 7.4x10-9 M) [57]
Description: In a GTPγS binding assay.
A-971432 Hs Agonist 6.4 pIC50 23
pIC50 6.4 (IC50 3.62x10-7 M) [23]
fingolimod Hs Agonist 6.1 pIC50 21
pIC50 6.1 (IC50 8.4x10-7 M) [21]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
SPM-354 Hs Antagonist 7.8 pA2 47
pA2 7.8 [47]
Description: In a β-arrestin assay.
NIBR-0213 Hs Antagonist 9.4 pKd 45
pKd 9.4 (Kd 3.7x10-10 M) [45]
VPC44116 Hs Antagonist 8.5 pKi 18
pKi 8.5 (Ki 3x10-9 M) [18]
VPC23019 Hs Antagonist 7.9 pKi 13
pKi 7.9 [13]
VPC03090-P Mm Antagonist 7.7 – 7.8 pKi 29
pKi 7.7 – 7.8 (Ki 2.13x10-8 – 1.4x10-8 M) [29]
VPC03090-P Hs Antagonist 7.6 – 7.7 pKi 29
pKi 7.6 – 7.7 (Ki 2.4x10-8 – 2.1x10-8 M) [29]
W146 Hs Antagonist 7.1 pKi 48
pKi 7.1 (Ki 7.7x10-8 M) [48]
NIBR-0213 Hs Antagonist 8.6 pIC50 45
pIC50 8.6 (IC50 2.5x10-9 M) [45]
VPC44116 Hs Antagonist 7.6 pIC50 18
pIC50 7.6 [18]
View species-specific antagonist tables
Immunopharmacology Comments
S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [24-25,49]. In human cord blood mast cells, S1P1R is required for migration but not for degranulation or cytokine and chemokine release [39,44]. S1P1R expression is elevated by allergen challenge in allergic rhinitis patients, but not in corticosteroid treated patients [35]. As a drug target selective S1P1R agonists are in development.
Immuno Cell Type Associations
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Comment:  B- and T-lymphocytes predominantly express S1P1 receptors, with S1P3 and S1P4 expressed at lower levels.
References:  53
Immuno Cell Type:  T cells
Cell Ontology Term:   alpha-beta T cell (CL:0000789)
Comment:  B- and T-lymphocytes predominantly express S1P1 receptors, with S1P3 and S1P4 expressed at lower levels.
References:  53
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
Comment:  Eosinophils express all S1P receptors except S1P2R.
References:  26
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
Comment:  Cord blood mast cells express S1P1R and S1P2R
References:  35
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  leukocyte chemotaxis (GO:0030595) IEA
T cell migration (GO:0072678) ISS
References: 
Immuno Process:  Chemotaxis & migration
Immuno Process ID:  10
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  leukocyte chemotaxis (GO:0030595) IEA
T cell migration (GO:0072678) ISS
References: 
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Phospholipase C stimulation
Calcium channel
Phospholipase D stimulation
Other - See Comments
Comments:  Involved in ERK phosphorylation [40] and stimulation of the PI3K/PKB and MEK/ERK pathways [9], and activation of Rac [16].
References:  10,30,38
Tissue Distribution
Brain, heart, lung, liver, spleen, kidney, thymus, and muscle
Species:  Mouse
Technique:  Northern blot
References:  58
Naive T cell and regulatory T cell
Species:  Mouse
Technique:  RT-PCR
References:  55
Bone marrow hematopoietic stem and progenitor cells
Species:  Mouse
Technique: 
References:  6
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Physiological Functions
S1P1 receptor is the predominant S1P receptor expressed on lymphocytesn and it is a major regulator of lymphocyte trafficking.
Species:  Human
Tissue: 
References:  50
Physiological Consequences of Altering Gene Expression
Embryonic lethality, defective vascular maturation due to lack of pericytes and alterations in signalling indicated by a decrease in Rac-mediated chemotaxis
Species:  Mouse
Tissue: 
Technique:  Gene targeting:- replacement vector, deletion of ORF, creation of s1p1–LacZ hybrid transcript
References:  34
Incomplete vascular maturation
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  3,34
Blockade in the egress of mature T-cells into the periphery in knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  1,37
Blockade of plasma cell homing and immature B cell migration in knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  2,28,43
Reduction of NKT cells distribution in peripheral tissues
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  4
Blockade of regulatory T cell differenciation in knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  33
Attenuation of autoimmune demyelination in astrocyte specific receptor knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  12
Loss of common lymphocyte progenitors.
Species:  Mouse
Tissue: 
Technique:  Bone marrow genetic overexpression.
References:  6
Attenuation of vascular inflammation.
Species:  Mouse
Tissue: 
Technique:  Endothelial cells Cre-mediated gene knockout.
References:  19
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
S1pr1tm1Rlp|S1pr2tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:99569  MP:0000260 abnormal angiogenesis PMID: 15138255 
S1pr1tm1Rlp|S1pr2tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MGI:99569  MP:0000260 abnormal angiogenesis PMID: 15138255 
S1pr1tm1Rlp|S1pr1tm2Rlp|Tg(Tek-cre)1Ywa S1pr1tm1Rlp/S1pr1tm2Rlp,Tg(Tek-cre)1Ywa/?
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1096355  MGI:2450309  MP:0009865 abnormal aorta smooth muscle morphology PMID: 15138255 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0001614 abnormal blood vessel morphology PMID: 11032855 
S1pr1tm1Rlp|S1pr1tm2Rlp|Tg(Tek-cre)1Ywa S1pr1tm1Rlp/S1pr1tm2Rlp,Tg(Tek-cre)1Ywa/?
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1096355  MGI:2450309  MP:0002127 abnormal cardiovascular system morphology PMID: 12869509 
S1pr1tm1Rlp|S1pr1tm2Rlp|Tg(Tek-cre)1Ywa S1pr1tm1Rlp/S1pr1tm2Rlp,Tg(Tek-cre)1Ywa/?
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1096355  MGI:2450309  MP:0001544 abnormal cardiovascular system physiology PMID: 12869509 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0003091 abnormal cell migration PMID: 11032855 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac
MGI:1096355  MP:0000830 abnormal diencephalon morphology PMID: 16314531 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac
MGI:1096355  MP:0000783 abnormal forebrain morphology PMID: 16314531 
S1pr1tm1.1Thla S1pr1tm1.1Thla/S1pr1tm1.1Thla
B6.Cg-S1pr1
MGI:1096355  MP:0003156 abnormal leukocyte migration PMID: 20584883 
S1pr1tm1Rlp|S1pr1tm2Rlp|Tg(Tek-cre)1Ywa S1pr1tm1Rlp/S1pr1tm2Rlp,Tg(Tek-cre)1Ywa/?
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1096355  MGI:2450309  MP:0002109 abnormal limb morphology PMID: 12869509 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0002109 abnormal limb morphology PMID: 11032855  15138255 
S1pr1tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MP:0002109 abnormal limb morphology PMID: 15138255 
S1pr1tm1.1Thla S1pr1tm1.1Thla/S1pr1tm1.1Thla
B6.Cg-S1pr1
MGI:1096355  MP:0003945 abnormal lymphocyte physiology PMID: 20584883 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac
MGI:1096355  MP:0008053 abnormal NK cell differentiation PMID: 19808259 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0003719 abnormal pericyte morphology PMID: 11032855 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac
MGI:1096355  MP:0000787 abnormal telencephalon morphology PMID: 16314531 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0006055 abnormal vascular endothelial cell morphology PMID: 11032855 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0005592 abnormal vascular smooth muscle morphology PMID: 11032855 
S1pr1tm1Rlp|S1pr1tm2Rlp|Tg(Tek-cre)1Ywa S1pr1tm1Rlp/S1pr1tm2Rlp,Tg(Tek-cre)1Ywa/?
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1096355  MGI:2450309  MP:0001718 abnormal yolk sac morphology PMID: 12869509 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0001718 abnormal yolk sac morphology PMID: 11032855 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac
MGI:1096355  MP:0008045 decreased NK cell number PMID: 19808259 
S1pr1tm1.1Thla S1pr1tm1.1Thla/S1pr1tm1.1Thla
B6.Cg-S1pr1
MGI:1096355  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 20584883 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0001785 edema PMID: 11032855 
S1pr1tm1Rlp|S1pr2tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:99569  MP:0006207 embryonic lethality during organogenesis PMID: 15138255 
S1pr1tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MP:0006207 embryonic lethality during organogenesis PMID: 15138255 
S1pr1tm1Rlp|S1pr2tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MGI:99569  MP:0006207 embryonic lethality during organogenesis PMID: 15138255 
S1pr1tm1Rlp|S1pr1tm2Rlp|Tg(Tek-cre)1Ywa S1pr1tm1Rlp/S1pr1tm2Rlp,Tg(Tek-cre)1Ywa/?
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1096355  MGI:2450309  MP:0000291 enlarged pericardium PMID: 12869509 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0000291 enlarged pericardium PMID: 11032855 
S1pr1tm1Rlp|S1pr1tm2Rlp|Tg(Tek-cre)1Ywa S1pr1tm1Rlp/S1pr1tm2Rlp,Tg(Tek-cre)1Ywa/?
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1096355  MGI:2450309  MP:0001914 hemorrhage PMID: 12869509 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0001914 hemorrhage PMID: 11032855  15138255 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac
MGI:1096355  MP:0001914 hemorrhage PMID: 16314531 
S1pr1tm1Rlp|S1pr2tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:99569  MP:0001914 hemorrhage PMID: 15138255 
S1pr1tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MP:0001914 hemorrhage PMID: 15138255 
S1pr1tm1Rlp|S1pr2tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MGI:99569  MP:0001914 hemorrhage PMID: 15138255 
S1pr1tm1.1Thla S1pr1tm1.1Thla/S1pr1tm1.1Thla
B6.Cg-S1pr1
MGI:1096355  MP:0008074 increased CD4-positive T cell number PMID: 20584883 
S1pr1tm1.1Thla S1pr1tm1.1Thla/S1pr1tm1.1Thla
B6.Cg-S1pr1
MGI:1096355  MP:0008078 increased CD8-positive T cell number PMID: 20584883 
S1pr1tm1Rlp|S1pr1tm2Rlp|Tg(Tek-cre)1Ywa S1pr1tm1Rlp/S1pr1tm2Rlp,Tg(Tek-cre)1Ywa/?
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1096355  MGI:2450309  MP:0006208 lethality throughout fetal growth and development PMID: 12869509 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0006208 lethality throughout fetal growth and development PMID: 11032855  15138255 
S1pr1tm2Rlp S1pr1tm2Rlp/S1pr1tm2Rlp
involves: 129S6/SvEvTac
MGI:1096355  MP:0002169 no abnormal phenotype detected PMID: 12869509 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0001787 pericardial edema PMID: 11032855 
S1pr1tm1Rlp|S1pr1tm2Rlp|Tg(Tek-cre)1Ywa S1pr1tm1Rlp/S1pr1tm2Rlp,Tg(Tek-cre)1Ywa/?
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1096355  MGI:2450309  MP:0000262 poor arterial differentiation PMID: 12869509 
S1pr1tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MP:0003814 vascular smooth muscle cell hypoplasia PMID: 11032855 

References

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1. Allende ML, Dreier JL, Mandala S, Proia RL. (2004) Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration. J. Biol. Chem.279 (15): 15396-401. [PMID:14732704]

2. Allende ML, Tuymetova G, Lee BG, Bonifacino E, Wu YP, Proia RL. (2010) S1P1 receptor directs the release of immature B cells from bone marrow into blood. J. Exp. Med.207 (5): 1113-24. [PMID:20404103]

3. Allende ML, Yamashita T, Proia RL. (2003) G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation. Blood102 (10): 3665-7. [PMID:12869509]

4. Allende ML, Zhou D, Kalkofen DN, Benhamed S, Tuymetova G, Borowski C, Bendelac A, Proia RL. (2008) S1P1 receptor expression regulates emergence of NKT cells in peripheral tissues. FASEB J.22 (1): 307-15. [PMID:17785606]

5. Ancellin N, Hla T. (1999) Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5. J. Biol. Chem.274 (27): 18997-9002. [PMID:10383399]

6. Blaho VA, Galvani S, Engelbrecht E, Liu C, Swendeman SL, Kono M, Proia RL, Steinman L, Han MH, Hla T. (2015) HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation. Nature523 (7560): 342-6. [PMID:26053123]

7. Bolli MH, Abele S, Binkert C, Bravo R, Buchmann S, Bur D, Gatfield J, Hess P, Kohl C, Mangold C et al.. (2010) 2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists. J. Med. Chem.53 (10): 4198-211. [PMID:20446681]

8. Brinkmann V, Davis MD, Heise CE, Albert R, Cottens S, Hof R, Bruns C, Prieschl E, Baumruker T, Hiestand P et al.. (2002) The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J. Biol. Chem.277 (24): 21453-7. [PMID:11967257]

9. Brizuela L, Rábano M, Gangoiti P, Narbona N, Macarulla JM, Trueba M, Gómez-Muñoz A. (2007) Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways. J. Lipid Res.48 (10): 2264-74. [PMID:17609523]

10. Brizuela L, Rábano M, Peña A, Gangoiti P, Macarulla JM, Trueba M, Gómez-Muñoz A. (2006) Sphingosine 1-phosphate: a novel stimulator of aldosterone secretion. J. Lipid Res.47 (6): 1238-49. [PMID:16554657]

11. Buzard DJ, Kim SH, Lopez L, Kawasaki A, Zhu X, Moody J, Thoresen L, Calderon I, Ullman B, Han S et al.. (2014) Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor. ACS Med Chem Lett5 (12): 1313-7. [PMID:25516790]

12. Choi JW, Gardell SE, Herr DR, Rivera R, Lee CW, Noguchi K, Teo ST, Yung YC, Lu M, Kennedy G et al.. (2011) FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proc. Natl. Acad. Sci. U.S.A.108 (2): 751-6. [PMID:21177428]

13. Davis MD, Clemens JJ, Macdonald TL, Lynch KR. (2005) Sphingosine 1-phosphate analogs as receptor antagonists. J. Biol. Chem.280 (11): 9833-41. [PMID:15590668]

14. Demont EH, Bailey JM, Bit RA, Brown JA, Campbell CA, Deeks N, Dowell SJ, Eldred C, Gaskin P, Gray JR et al.. (2016) Discovery of Tetrahydropyrazolopyridine as Sphingosine 1-Phosphate Receptor 3 (S1P3)-Sparing S1P1 Agonists Active at Low Oral Doses. J. Med. Chem.59 (3): 1003-20. [PMID:26751273]

15. Deng Q, Clemas JA, Chrebet G, Fischer P, Hale JJ, Li Z, Mills SG, Bergstrom J, Mandala S, Mosley R et al.. (2007) Identification of Leu276 of the S1P1 receptor and Phe263 of the S1P3 receptor in interaction with receptor specific agonists by molecular modeling, site-directed mutagenesis, and affinity studies. Mol. Pharmacol.71 (3): 724-35. [PMID:17170199]

16. Faroudi M, Hons M, Zachacz A, Dumont C, Lyck R, Stein JV, Tybulewicz VL. (2010) Critical roles for Rac GTPases in T-cell migration to and within lymph nodes. Blood116 (25): 5536-47. [PMID:20870900]

17. Forrest M, Sun SY, Hajdu R, Bergstrom J, Card D, Doherty G, Hale J, Keohane C, Meyers C, Milligan J et al.. (2004) Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J. Pharmacol. Exp. Ther.309 (2): 758-68. [PMID:14747617]

18. Foss FW, Snyder AH, Davis MD, Rouse M, Okusa MD, Lynch KR, Macdonald TL. (2007) Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists. Bioorg. Med. Chem.15 (2): 663-77. [PMID:17113298]

19. Galvani S, Sanson M, Blaho VA, Swendeman SL, Obinata H, Conger H, Dahlbäck B, Kono M, Proia RL, Smith JD et al.. (2015) HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation. Sci Signal8 (389): ra79. [PMID:26268607]

20. Gonzalez-Cabrera PJ, Jo E, Sanna MG, Brown S, Leaf N, Marsolais D, Schaeffer MT, Chapman J, Cameron M, Guerrero M et al.. (2008) Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like headgroup interactions. Mol. Pharmacol.74 (5): 1308-18. [PMID:18708635]

21. Hale JJ, Lynch CL, Neway W, Mills SG, Hajdu R, Keohane CA, Rosenbach MJ, Milligan JA, Shei GJ, Parent SA et al.. (2004) A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonists. J. Med. Chem.47 (27): 6662-5. [PMID:15615513]

22. Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G, Desale H, Clemons B, Cahalan SM, Schuerer SC et al.. (2012) Crystal structure of a lipid G protein-coupled receptor. Science335 (6070): 851-5. [PMID:22344443]

23. Hobson AD, Harris CM, van der Kam EL, Turner SC, Abibi A, Aguirre AL, Bousquet P, Kebede T, Konopacki DB, Gintant G et al.. (2015) Discovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P5) Agonist for the Potential Treatment of Neurodegenerative Disorders. J. Med. Chem.58 (23): 9154-70. [PMID:26509640]

24. Högenauer K, Billich A, Pally C, Streiff M, Wagner T, Welzenbach K, Nussbaumer P. (2008) Phosphorylation by sphingosine kinase 2 is essential for in vivo potency of FTY720 analogues. ChemMedChem3 (7): 1027-9. [PMID:18383466]

25. Idzko M, Hammad H, van Nimwegen M, Kool M, Müller T, Soullié T, Willart MA, Hijdra D, Hoogsteden HC, Lambrecht BN. (2006) Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. J. Clin. Invest.116 (11): 2935-44. [PMID:17080194]

26. Idzko M, Panther E, Corinti S, Morelli A, Ferrari D, Herouy Y, Dichmann S, Mockenhaupt M, Gebicke-Haerter P, Di Virgilio F et al.. (2002) Sphingosine 1-phosphate induces chemotaxis of immature and modulates cytokine-release in mature human dendritic cells for emergence of Th2 immune responses. FASEB J.16 (6): 625-7. [PMID:11919175]

27. Im DS, Clemens J, Macdonald TL, Lynch KR. (2001) Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): structure-activity relationship of sphingosine1-phosphate receptors. Biochemistry40 (46): 14053-60. [PMID:11705398]

28. Kabashima K, Haynes NM, Xu Y, Nutt SL, Allende ML, Proia RL, Cyster JG. (2006) Plasma cell S1P1 expression determines secondary lymphoid organ retention versus bone marrow tropism. J. Exp. Med.203 (12): 2683-90. [PMID:17101733]

29. Kennedy PC, Zhu R, Huang T, Tomsig JL, Mathews TP, David M, Peyruchaud O, Macdonald TL, Lynch KR. (2011) Characterization of a sphingosine 1-phosphate receptor antagonist prodrug. J. Pharmacol. Exp. Ther.338 (3): 879-89. [PMID:21632869]

30. Kon J, Sato K, Watanabe T, Tomura H, Kuwabara A, Kimura T, Tamama K, Ishizuka T, Murata N, Kanda T et al.. (1999) Comparison of intrinsic activities of the putative sphingosine 1-phosphate receptor subtypes to regulate several signaling pathways in their cDNA-transfected Chinese hamster ovary cells. J. Biol. Chem.274 (34): 23940-7. [PMID:10446161]

31. Lee MJ, Thangada S, Liu CH, Thompson BD, Hla T. (1998) Lysophosphatidic acid stimulates the G-protein-coupled receptor EDG-1 as a low affinity agonist. J. Biol. Chem.273 (34): 22105-12. [PMID:9705355]

32. Li Z, Chen W, Hale JJ, Lynch CL, Mills SG, Hajdu R, Keohane CA, Rosenbach MJ, Milligan JA, Shei GJ et al.. (2005) Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3. J. Med. Chem.48 (20): 6169-73. [PMID:16190743]

33. Liu G, Burns S, Huang G, Boyd K, Proia RL, Flavell RA, Chi H. (2009) The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat. Immunol.10 (7): 769-77. [PMID:19483717]

34. Liu Y, Wada R, Yamashita T, Mi Y, Deng CX, Hobson JP, Rosenfeldt HM, Nava VE, Chae SS, Lee MJ et al.. (2000) Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J. Clin. Invest.106 (8): 951-61. [PMID:11032855]

35. Mackle T, Gendy SS, Walsh M, McConn-Walsh R, Costello RW, Walsh MT. (2008) Role of sphingosine 1-phosphate receptor expression in eosinophils of patients with allergic rhinitis, and effect of topical nasal steroid treatment on this receptor expression. J Laryngol Otol122 (12): 1309-17. [PMID:18808729]

36. Martinborough E, Boehm MF, Yeager AR, Tamiya J, Huang L, Brahmachary E, Moorjani M, Timony GA, Brooks JL, Peach R et al.. (2011) Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis. Patent number: US20110172202 A1. Assignee: Martinborough E, Boehm MF, Yeager AR, Tamiya J, Huang L, Brahmachary E, Moorjani M, Timony GA, Brooks JL, Peach R et al.. Priority date: 13/11/2009. Publication date: 14/07/2011.

37. Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, Allende ML, Proia RL, Cyster JG. (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature427 (6972): 355-60. [PMID:14737169]

38. Okamoto H, Takuwa N, Gonda K, Okazaki H, Chang K, Yatomi Y, Shigematsu H, Takuwa Y. (1998) EDG1 is a functional sphingosine-1-phosphate receptor that is linked via a Gi/o to multiple signaling pathways, including phospholipase C activation, Ca2+ mobilization, Ras-mitogen-activated protein kinase activation, and adenylate cyclase inhibition. J. Biol. Chem.273 (42): 27104-10. [PMID:9765227]

39. Olivera A. (2008) Unraveling the complexities of sphingosine-1-phosphate function: the mast cell model. Prostaglandins Other Lipid Mediat.86 (1-4): 1-11. [PMID:18403224]

40. Osinde M, Mullershausen F, Dev KK. (2007) Phosphorylated FTY720 stimulates ERK phosphorylation in astrocytes via S1P receptors. Neuropharmacology52 (5): 1210-8. [PMID:17379261]

41. Pan S, Gray NS, Gao W, Mi Y, Fan Y, Wang X, Tuntland T, Che J, Lefebvre S, Chen Y et al.. (2013) Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator. ACS Med Chem Lett4 (3): 333-7. [PMID:24900670]

42. Pan S, Mi Y, Pally C, Beerli C, Chen A, Guerini D, Hinterding K, Nuesslein-Hildesheim B, Tuntland T, Lefebvre S et al.. (2006) A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model. Chem. Biol.13 (11): 1227-34. [PMID:17114004]

43. Pereira JP, Xu Y, Cyster JG. (2010) A role for S1P and S1P1 in immature-B cell egress from mouse bone marrow. PLoS ONE5 (2): e9277. [PMID:20174580]

44. Price MM, Oskeritzian CA, Milstien S, Spiegel S. (2008) Sphingosine-1-phosphate synthesis and functions in mast cells. Future Lipidol3 (6): 665-674. [PMID:19802381]

45. Quancard J, Bollbuck B, Janser P, Angst D, Berst F, Buehlmayer P, Streiff M, Beerli C, Brinkmann V, Guerini D et al.. (2012) A potent and selective S1P(1) antagonist with efficacy in experimental autoimmune encephalomyelitis. Chem. Biol.19 (9): 1142-51. [PMID:22999882]

46. Sanna MG, Liao J, Jo E, Alfonso C, Ahn MY, Peterson MS, Webb B, Lefebvre S, Chun J, Gray N et al.. (2004) Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J. Biol. Chem.279 (14): 13839-48. [PMID:14732717]

47. Sanna MG, Vincent KP, Repetto E, Nguyen N, Brown SJ, Abgaryan L, Riley SW, Leaf NB, Cahalan SM, Kiosses WB et al.. (2016) Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and Genetic Evidence for Direct S1P3 Regulation of Mouse Cardiac Conduction. Mol. Pharmacol.89 (1): 176-86. [PMID:26494861]

48. Sanna MG, Wang SK, Gonzalez-Cabrera PJ, Don A, Marsolais D, Matheu MP, Wei SH, Parker I, Jo E, Cheng WC et al.. (2006) Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nat. Chem. Biol.2 (8): 434-41. [PMID:16829954]

49. Sawicka E, Zuany-Amorim C, Manlius C, Trifilieff A, Brinkmann V, Kemeny DM, Walker C. (2003) Inhibition of Th1- and Th2-mediated airway inflammation by the sphingosine 1-phosphate receptor agonist FTY720. J. Immunol.171 (11): 6206-14. [PMID:14634137]

50. Schwab SR, Cyster JG. (2007) Finding a way out: lymphocyte egress from lymphoid organs. Nat. Immunol.8 (12): 1295-301. [PMID:18026082]

51. Scott FL, Clemons B, Brooks J, Brahmachary E, Powell R, Dedman H, Desale HG, Timony GA, Martinborough E, Rosen H et al.. (2016) Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity. Br. J. Pharmacol.173 (11): 1778-92. [PMID:26990079]

52. Song J, Matsuda C, Kai Y, Nishida T, Nakajima K, Mizushima T, Kinoshita M, Yasue T, Sawa Y, Ito T. (2008) A novel sphingosine 1-phosphate receptor agonist, 2-amino-2-propanediol hydrochloride (KRP-203), regulates chronic colitis in interleukin-10 gene-deficient mice. J. Pharmacol. Exp. Ther.324 (1): 276-83. [PMID:17898319]

53. Subei AM, Cohen JA. (2015) Sphingosine 1-phosphate receptor modulators in multiple sclerosis. CNS Drugs29 (7): 565-75. [PMID:26239599]

54. Sugahara K, Maeda Y, Shimano K, Mogami A, Kataoka H, Ogawa K, Hikida K, Kumagai H, Asayama M, Yamamoto T et al.. (2017) Amiselimod, a novel sphingosine 1-phosphate receptor-1 modulator, has potent therapeutic efficacy for autoimmune diseases, with low bradycardia risk. Br. J. Pharmacol.174 (1): 15-27. [PMID:27714763]

55. Wang W, Graeler MH, Goetzl EJ. (2004) Physiological sphingosine 1-phosphate requirement for optimal activity of mouse CD4+ regulatory T Cells. FASEB J.18 (9): 1043-5. [PMID:15084513]

56. Yamamoto D, Ikeshita N, Daito R, Herningtyas EH, Toda K, Takahashi K, Iida K, Takahashi Y, Kaji H, Chihara K, Okimura Y. (2007) Neither intravenous nor intracerebroventricular administration of obestatin affects the secretion of GH, PRL, TSH and ACTH in rats. Regul. Pept.138 (2-3): 141-4. [PMID:17055593]

57. Yamamoto R, Okada Y, Hirose J, Koshika T, Kawato Y, Maeda M, Saito R, Hattori K, Harada H, Nagasaka Y et al.. (2014) ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile. PLoS ONE9 (10): e110819. [PMID:25347187]

58. Zhang G, Contos JJ, Weiner JA, Fukushima N, Chun J. (1999) Comparative analysis of three murine G-protein coupled receptors activated by sphingosine-1-phosphate. Gene227 (1): 89-99. [PMID:9931453]

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Jerold Chun, Victoria Blaho, Yasuyuki Kihara, Chido Mpamhanga.
Lysophospholipid (S1P) receptors: S1P1 receptor. Last modified on 16/05/2017. Accessed on 18/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=275.