Affinage

S1PR3

Sphingosine 1-phosphate receptor 3 · UniProt Q99500

Length
378 aa
Mass
42.2 kDa
Annotated
2026-04-28
85 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

S1PR3 is a G protein-coupled receptor for sphingosine 1-phosphate that transduces signals through Gi, Gq, and G12/13 heterotrimeric G proteins, activating PLC/Ca²⁺, PI3K/Akt (via PLD2), Rac, Rho, ERK/MAPK, and NF-κB pathways to regulate diverse cellular responses including migration, proliferation, survival, and metabolic reprogramming (PMID:10488065, PMID:10617617, PMID:11468290, PMID:11673450). The crystal structure of the active S1PR3–S1P complex reveals the ligand in an unbent conformation within a transmembrane tunnel, where a 'quartet core' of residues undergoes coordinated rotamer changes that control both receptor activation and G protein subtype selectivity (PMID:34108205). Physiologically, S1PR3 drives endothelial cell migration through Rho-dependent integrin clustering (PMID:11150298), macrophage bactericidal function via VPS34 recruitment to phagosomes (PMID:28850247), sensory neuron activation of itch and pain through TRPA1 and TRPV1 channels respectively (PMID:30082422), cardiac IK.ACh current activation in atrial myocytes (PMID:10908314), and cancer stem cell expansion via Notch signaling (PMID:25254944). S1PR3 also participates in a positive feedback loop in keratinocytes where Gαi/PKA–Src–STAT3 signaling upregulates S1PR3 expression, contributing to psoriasis-like inflammation (PMID:39833165).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 High

    Establishing S1PR3 as a multi-G-protein-coupled S1P receptor resolved how a single lipid could activate divergent intracellular pathways through different receptor subtypes, distinguishing S1PR3 (Gi/Gq/G13 coupling) from S1PR1 (Gi-only).

    Evidence Subunit-selective [³⁵S]GTPγS binding in Sf9/HEK293 cells, Ca²⁺ transients in Xenopus oocytes, radioligand binding and IP/cAMP assays in CHO cells

    PMID:10381367 PMID:10383399 PMID:10488065 PMID:9928946

    Open questions at the time
    • Structural basis of differential G protein selectivity unknown
    • Relative contribution of each G protein arm in native tissues not established
  2. 2001 High

    Delineating the downstream effector architecture showed that S1PR3 preferentially couples to PLC/Ca²⁺ (confirmed by genetic knockout with rescue), activates PI3K/Akt through PLD2, and mediates NF-κB activation through PKC/Ca²⁺, while also activating Rho/Rac for migration and integrin clustering in endothelial cells.

    Evidence S1PR3-KO MEFs with retroviral rescue; dominant-negative PLD2 in CHO cells; NF-κB reporter with PKC/Ca²⁺ inhibition in HEK293; antisense knockdown with Rho/integrin assays in HUVECs

    PMID:11094076 PMID:11150298 PMID:11443127 PMID:11468290 PMID:11673450

    Open questions at the time
    • Mechanism of PLD2 coupling to S1PR3 not determined
    • Whether Rho activation is direct through G13 or indirect in endothelial cells not resolved
  3. 2000 High

    Discovery that S1PR3 activates cardiac IK.ACh in human atrial myocytes established a physiological role beyond cell lines, showing receptor-mediated ion channel regulation in native tissue.

    Evidence Patch-clamp electrophysiology with suramin blockade in freshly isolated atrial cardiomyocytes

    PMID:10908314

    Open questions at the time
    • Whether S1PR3-mediated IK.ACh contributes to cardiac arrhythmogenesis not tested
    • Downstream G protein subtype mediating the ionic effect not identified
  4. 2002 High

    S1PR2/S1PR3 double-knockout epistasis revealed that S1PR3 preferentially drives PLC/Ca²⁺ while S1PR2 preferentially drives Rho, and that their combined loss causes perinatal lethality, establishing essential combined developmental roles.

    Evidence Double-KO mice with MEF signaling assays for Rho, PLC, Ca²⁺, and adenylyl cyclase

    PMID:12006579

    Open questions at the time
    • Cause of perinatal lethality not characterized
    • Organ-specific contributions of each receptor not dissected
  5. 2006 Medium

    Linking S1PR3 to estrogen-EGFR transactivation in breast cancer and VEGF-dependent Akt3 induction in endothelial cells placed S1PR3 at the intersection of growth factor and sphingolipid signaling networks.

    Evidence SphK1 activation/S1P release leading to EGFR phosphorylation via MMP in breast cancer cells; siRNA knockdown showing VEGF-S1PR3-Akt3 axis in primary endothelial cells

    PMID:16527273 PMID:16636149

    Open questions at the time
    • Direct physical interaction between S1PR3 and EGFR not demonstrated
    • Physiological relevance in vivo for estrogen-EGFR axis not established
  6. 2014 Medium

    Identification of S1PR3 as a driver of cancer stem cell expansion via ligand-independent Notch activation revealed a non-canonical signaling mechanism, with in vivo validation showing S1PR3 loss reduces tumorigenicity.

    Evidence ALDH flow cytometry, S1PR3 siRNA/antagonist, Notch activation assay, nude mouse xenograft

    PMID:25254944

    Open questions at the time
    • Mechanism of ligand-independent Notch activation by S1PR3 not defined
    • Whether direct S1PR3-Notch physical interaction occurs not tested
  7. 2017 High

    Demonstration that S1PR3 controls macrophage bactericidal function by recruiting VPS34 to phagosomes for ROS production and phagosome maturation established a direct role in innate immunity, with S1PR3-KO mice showing increased bacterial burden and sepsis mortality.

    Evidence S1PR3-KO mice, bone marrow transfer, bacterial killing assay, VPS34 recruitment to phagosomes

    PMID:28850247

    Open questions at the time
    • How S1PR3 signaling connects to VPS34 recruitment molecularly unknown
    • Whether specific G protein arm mediates phagosome function not defined
  8. 2018 High

    Genetic studies in knockout mice revealed that S1PR3 mediates S1P-induced itch via TRPA1 in pruriceptors and pain via TRPV1 in nociceptors, establishing cell-type-specific coupling to distinct TRP channels as the basis for dual somatosensory functions.

    Evidence Ca²⁺ imaging and electrophysiology in sensory neurons; behavioral assays in S1PR3-KO, TRPA1-KO, and TRPV1-KO mice

    PMID:30082422

    Open questions at the time
    • Intracellular signaling cascade linking S1PR3 to TRPA1 versus TRPV1 activation not resolved
    • Whether PLC or other second messengers gate TRP channels downstream of S1PR3 not established
  9. 2018 Medium

    S1PR3 was shown to promote aerobic glycolysis in osteosarcoma through YAP nuclear translocation and YAP-c-MYC complex formation driving PGAM1 transcription, broadening S1PR3's role to metabolic reprogramming in cancer.

    Evidence Co-IP of YAP-c-MYC, ChIP on PGAM1 promoter, metabolic flux analysis, xenograft model

    PMID:30587459

    Open questions at the time
    • Whether S1PR3-YAP axis operates through Hippo kinase inhibition or parallel pathway not determined
    • Generalizability to other cancer types not tested
  10. 2021 High

    The crystal structure of active S1PR3 bound to S1P resolved how the ligand adopts an unbent conformation in a transmembrane tunnel and identified a 'quartet core' of residues whose coordinated rotamer changes control both receptor activation and G protein subtype selectivity, providing a structural basis for the multi-G-protein coupling first observed in 1999.

    Evidence X-ray crystallography at 3.2 Å resolution; mutagenesis of quartet core residues; structural comparison with inactive S1PR1

    PMID:34108205

    Open questions at the time
    • Cryo-EM structure of S1PR3-G protein ternary complex not yet obtained
    • How quartet core conformational changes propagate to the intracellular G protein binding surface not resolved
  11. 2025 Medium

    Discovery of a Gαi/PKA–Src–STAT3 positive feedback loop where STAT3 directly upregulates S1PR3 transcription in keratinocytes revealed an autoamplification mechanism relevant to psoriasis-like inflammation, and S1PR3's regulation of hippocampal synaptic plasticity via RhoA/ROCK1 was established.

    Evidence S1PR3 genetic deletion/pharmacological inhibition with STAT3 ChIP on S1PR3 promoter in skin inflammation model; AAV-mediated S1PR3 overexpression with RhoA rescue in hippocampal neurons

    PMID:39828081 PMID:39833165

    Open questions at the time
    • Whether the STAT3 feedback loop operates in cell types beyond keratinocytes not tested
    • Direct assessment of S1PR3 in human psoriasis tissue not performed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the cryo-EM structure of S1PR3 in complex with different G protein subtypes, the molecular mechanism linking S1PR3 to VPS34 phagosomal recruitment, how cell-type-specific G protein coupling is determined, and whether biased agonism at S1PR3 can be therapeutically exploited.
  • No ternary complex structure of S1PR3 with any G protein
  • Mechanism of cell-type-specific effector selection unknown
  • No clinical data on S1PR3-selective therapeutics

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-112316 Neuronal System 3 R-HSA-168256 Immune System 3 R-HSA-1430728 Metabolism 2
Partners
GNA13GNAI1GNAQPLD2STAT3TRPA1TRPV1VPS34

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 S1PR3 (EDG-3) couples to Gi, Gq, and G13 families of heterotrimeric G proteins, in contrast to S1PR1 (EDG-1) which couples only to Gi. This was demonstrated directly using a subunit-selective [35S]GTPgammaS binding assay in Sf9 and HEK293 cells. Subunit-selective [35S]GTPgammaS binding assay in Sf9 and HEK293 cells The Journal of biological chemistry High 10488065
1999 S1PR3 (EDG-3) expressed in Xenopus oocytes confers SPP-responsive intracellular calcium transients coupled to Gq pathway; suramin selectively antagonizes SPP-activated calcium responses in EDG-3-expressing oocytes with IC50 of 22 µM, establishing EDG-3 as a pharmacologically distinct GPCR subtype. Xenopus oocyte expression system; Ca2+ measurements; chimeric Galphaqi co-expression The Journal of biological chemistry High 10383399
1999 S1PR3 (EDG-3) overexpression confers specific [32P]S1P binding (displaced by S1P and sphingosylphosphorylcholine but not LPA), mediates inositol phosphate production and [Ca2+]i increase partially sensitive to pertussis toxin, activates MAPK in PTX-sensitive/Ras-dependent manner, and decreases cellular cAMP, establishing distinct signaling characteristics compared to EDG-1 and EDG-5. Radioligand binding, inositol phosphate assay, Ca2+ measurements, MAPK activation assay, cAMP measurement in EDG-3-overexpressing cells Biochemical and biophysical research communications High 10381367
1999 S1PR3 (EDG-3) activates the phospholipase C-Ca2+ system in transfected CHO cells; S1P-induced Ca2+ response was enhanced and associated with significant inositol phosphate production in EDG-3-transfected versus vector-transfected cells, inhibited by the PLC inhibitor U73122. Ca2+ measurement and inositol phosphate assay in EDG-3-transfected CHO cells FEBS letters High 9928946
2000 S1PR3 (EDG-3) expressed in CHO cells promotes S1P-induced chemotaxis and membrane ruffling via PI3K- and Rac-dependent mechanisms, inducing a biphasic increase in GTP-bound Rac; this is in contrast to EDG-5 which inhibits Rac activation. Chemotaxis assay, membrane ruffling imaging, Rac-GTP pulldown in CHO cells expressing EDG-3 Molecular and cellular biology High 11094076
2001 S1PR3 (EDG-3) is required together with EDG-1 for S1P-induced Rho activation and integrin (αvβ3 and β1) clustering into focal contacts in human umbilical vein endothelial cells; antisense knockdown of EDG-3 inhibits S1P-induced cell migration on fibronectin, vitronectin and Matrigel. Antisense phosphothioate oligonucleotides, C3 exotoxin inhibition, integrin blocking antibodies, Rho activation assay, HUVEC migration assay The Journal of biological chemistry High 11150298
2001 S1PR3 (LP(B3)/EDG-3) deletion in mouse embryonic fibroblasts causes significant decreases in S1P-induced phospholipase C activation and slight decreases in adenylyl cyclase inhibition, with no change in Rho activation, demonstrating nonredundant coupling of S1PR3 to PLC/Ca2+ pathway; retroviral re-expression of LP(B3) rescued PLC activation. Gene knockout in mice, MEF preparation, PLC activation assay, adenylyl cyclase inhibition assay, Rho activation assay, retroviral rescue The Journal of biological chemistry High 11443127
2002 In S1P2/S1P3 double-knockout MEFs, Rho activation is completely lost and PLC activation and calcium mobilization are significantly decreased compared to wild-type, establishing preferential coupling of S1PR3 to PLC/Ca2+ pathways and S1PR2 to Rho; double-null pups show perinatal lethality demonstrating essential combined role. Double gene knockout in mice, MEF signaling assays (Rho, PLC, Ca2+, adenylyl cyclase) The Journal of biological chemistry High 12006579
2001 S1PR3 (EDG-3) and EDG-5, but not EDG-1, mediate S1P-induced NF-κB activation in HEK293 cells through a mechanism requiring protein kinase C and Ca2+ downstream of Gq; Rho activation alone through Gq or G13 is insufficient for NF-κB activation. NF-κB reporter assay, PKC inhibitor treatment, Ca2+ chelation, overexpression of EDG receptor subtypes in HEK293 cells The Journal of biological chemistry High 11673450
2001 S1PR3 (EDG-3) mediates S1P-induced PI3K and Akt activation in CHO cells through phospholipase D; PLD2 is required downstream of EDG-3, as catalytically inactive PLD2 mutant eliminates S1P-induced Akt activation, and 1-butanol (PLD inhibitor) blocks PI3K/Akt activation and Rac-dependent membrane ruffling. PLD activity assay, PI3K assay, Akt phosphorylation, dominant-negative PLD2 co-expression, 1-butanol inhibition in EDG-3-overexpressing CHO cells The Journal of biological chemistry High 11468290
2000 S1PR3 (EDG-3) mediates S1P-induced cell proliferation, survival, ERK/MAP kinase activation, and c-Jun/c-Fos induction via Gi/o- and Rho-dependent pathways; pertussis toxin and C3 exoenzyme inhibit EDG-3-mediated serum response element activation. Stable transfection in HTC4 hepatoma cells, thymidine incorporation, apoptosis assay, ERK activation, reporter gene assay, PTX and C3 exoenzyme inhibition The Journal of biological chemistry High 10617617
2000 S1PR3 (EDG-3) mediates S1P-induced activation of IK.ACh (muscarinic-type inward rectifier K+ current) in human atrial cardiomyocytes; this is blocked by the EDG-3-selective antagonist suramin but not affected by carbachol, and EDG-3 transcript is detected in human atrial cells. Patch-clamp electrophysiology in freshly isolated atrial myocytes, suramin antagonist, RT-PCR for receptor transcripts Molecular pharmacology High 10908314
2003 A synthetic peptide (KRX-725) from the second intracellular loop of S1PR3 mimics S1P by triggering Gi-dependent MEK-ERK signaling, induces receptor internalization of S1PR3 but not S1PR1, and promotes angiogenesis ex vivo and in vivo; demonstrating that the second intracellular loop of S1PR3 is sufficient to activate specific downstream signaling. Peptide synthesis, ERK activation assay, receptor internalization assay, aortic ring ex vivo angiogenesis, mouse corneal pocket assay Blood Medium 12763936
2002 S1PR3 (EDG-3) mediates S1P-induced Ca2+ mobilization in C2C12 myoblasts; antisense oligodeoxynucleotides against EDG-3 significantly reduced SPP-induced Ca2+ response, and combined inhibition of EDG-3 and EDG-5 abolished the response, whereas antisense against EDG-1 had no effect. Antisense ODN knockdown, Ca2+ imaging (confocal, spectrophotofluorimeter) in C2C12 myoblasts The Biochemical journal Medium 11853542
2006 Estrogen (E2) transactivates EGFR in breast cancer cells via a mechanism involving SphK1 activation, S1P release, and subsequent activation of S1PR3 (EDG-3), which leads to EGFR transactivation in a matrix metalloprotease-dependent manner. SphK1 activity assay, S1P ELISA, S1PR3 signaling assay, EGFR phosphorylation, MMP inhibitor treatment in breast cancer cells The Journal of cell biology Medium 16636149
2006 S1PR3 (Edg3/S1P3) expression is necessary and sufficient for VEGF-dependent upregulation of Akt3 in primary endothelial cells; VEGF stimulates S1P3 expression via a Gi-protein-dependent mechanism (pertussis toxin-sensitive), and knockdown of S1P3 blocks VEGF-stimulated Akt3 induction. siRNA knockdown, pertussis toxin inhibition, Akt3 mRNA/protein measurement, overexpression in primary endothelial cells Experimental cell research Medium 16527273
2014 S1PR3 mediates S1P-induced expansion of cancer stem cells (ALDH-positive) via ligand-independent Notch activation; S1PR3 knockdown or S1PR3 antagonist inhibits tumorigenicity of SphK1-overexpressing CSCs in nude mice. ALDH flow cytometry, S1PR3 siRNA knockdown, S1PR3 antagonist, xenograft mouse model, Notch pathway activation assay Nature communications Medium 25254944
2015 S1PR3 contributes to the egress of Gna13-mutant germinal center B cells from lymph nodes; dissemination of Gna13-deficient GC B cells in mouse models depends on S1PR3, placing S1PR3 downstream of Gα13 signaling in GC B cell retention/egress. Genetic mouse models (Gna13 conditional KO, S1PR3 KO), lymph node egress assays, flow cytometry The Journal of experimental medicine Medium 26573295
2017 S1PR3 is required for macrophage bactericidal function in sepsis; S1pr3-/- mice show increased bacterial burden and mortality; S1PR3 regulates ROS production and phagosome maturation by controlling recruitment of VPS34 (vacuolar protein-sorting 34) to phagosomes. S1PR3 knockout mice, bone marrow transfer, bacterial killing assay, ROS measurement, phagosome maturation assay, VPS34 recruitment to phagosomes American journal of respiratory and critical care medicine High 28850247
2017 S1PR3 is a direct target of miR-127 in myogenic cells; overexpression of miR-127 enhances myogenic differentiation and S1PR3 is required for this effect, as S1PR3 knockdown mimics miR-127 overexpression and S1PR3 restoration reverses the pro-differentiation phenotype. miRNA overexpression, luciferase reporter assay, C2C12 differentiation assay, transgenic mice, satellite cell assays Cell death & disease Medium 28358363
2018 S1PR3 signals via TRPA1 to mediate S1P-induced itch in pruriceptors, and via TRPV1 to mediate S1P-induced pain in nociceptors; S1P-evoked itch is lost in TRPA1-null mice and pain/heat hypersensitivity is lost in TRPV1-null mice, with S1PR3 required for both responses. Ca2+ imaging, electrophysiology in sensory neurons, S1PR3-KO mice, TRPA1-KO and TRPV1-KO mice, behavioral itch and pain assays The Journal of neuroscience High 30082422
2018 S1P/S1PR3 axis promotes aerobic glycolysis in osteosarcoma by inhibiting YAP phosphorylation and promoting YAP nuclear translocation, leading to formation of a YAP-c-MYC complex that enhances PGAM1 transcription; co-immunoprecipitation confirmed YAP-c-MYC interaction and ChIP showed their binding to PGAM1 promoter. S1PR3 knockdown, co-immunoprecipitation, chromatin immunoprecipitation, luciferase reporter, metabolic flux analysis, xenograft mouse model EBioMedicine Medium 30587459
2019 S1PR3 activation in mouse vagal airway afferent nodose C-fibers mediates S1P-induced action potential generation; S1P fails to activate airway nodose C-fibers in S1PR3 knockout mice, and an S1PR3 antagonist (TY52156) inhibits S1P-evoked action potentials. Single-cell RT-PCR, two-photon Ca2+ imaging of nodose ganglia in transgenic GCaMP6s mice, single-fiber electrophysiology, S1PR3-KO mice, S1PR3 antagonist The Journal of physiology High 30793318
2021 Crystal structure of active human S1PR3 in complex with its natural agonist S1P determined at 3.2-Å resolution; S1P adopts an unbent conformation in a long tunnel traversing the receptor obliquely; four residues surrounding the alkyl tail of S1P (the 'quartet core') undergo coordinated rotamer changes to accommodate S1P and induce active conformation; the quartet core also determines G protein selectivity of S1PR3. X-ray crystallography, active S1PR3-S1P complex structure at 3.2 Å; mutagenesis of quartet core residues; comparison with inactive S1PR1 structure Science advances High 34108205
2021 S1PR3 is a G12-biased agonist target; ALESIA compound acts as an S1PR3-G12-biased agonist (identified by TGFα shedding assay), promoting nitric oxide production and oxidative stress leading to cancer cell death under low-glucose conditions. TGFα shedding assay (DREADD-based G protein activation), nitric oxide measurement, oxidative stress assay, NADPH measurement, in vivo peritoneal tumor model Cell chemical biology Medium 33561428
2020 S1P lyase inhibition protects against sepsis by increasing S1P levels that stimulate S1PR3, activating p38 and ERK MAPK pathways, reducing tissue damage; the protective effects are absent in S1PR3-deficient mice, establishing S1PR3 as essential for this protective pathway. S1P lyase inhibitor treatment, S1PR3-KO mice, cytokine measurement, lung permeability assay, p38/ERK phosphorylation, survival studies EBioMedicine Medium 32711251
2009 EDG3 (S1PR3) protein co-immunoprecipitates with SHC3 protein from human ependymoma tissue, and EDG3 protein was found to be N-glycosylated (confirmed by N-glycosidase-F digestion), indicating proper post-translational processing and plasma membrane trafficking. Co-immunoprecipitation from tumor tissue, N-glycosidase-F digestion, qPCR gene amplification analysis Cancer letters Low 19748727
2018 S1PR3 mediates S1P-induced CCL20 release from human bronchial epithelial cells; siRNA knockdown of S1PR3 suppresses S1P-induced CCL20 expression, and S1PR1/3 antagonist VPC23019 attenuates eosinophilic inflammation in OVA-challenged mice. Transcriptome analysis, siRNA knockdown, ELISA, OVA-challenged asthma mouse model, VPC23019 antagonist PloS one Medium 30192865
2018 S1PR3 mediates fingolimod phosphate (pFTY720)-dependent protection of astrocytes against OGD-induced neuroinflammation by inhibiting TLR2/4-PI3K-NFκB signaling; S1PR3 knockdown reverses the protective effects of pFTY720. S1PR3 siRNA knockdown, OGD model in astrocytes, TLR2/PI3K/NFκB pathway assays, cytokine measurement Journal of cellular and molecular medicine Medium 29536648
2019 FTY720-P stimulates the Na+/K+ ATPase in HepG2 liver cells via S1PR3, acting sequentially through PKC, ERK, NF-κB, and COX-2 to induce PGE2 release; the effect was blocked by the specific S1PR3 antagonist CAY10444 and reproduced by the S1PR3 agonist CYM5541. Na+/K+ ATPase activity assay, S1PR3-specific antagonist and agonist, PKC/ERK inhibitors, COX inhibitor, IκB expression western blot in HepG2 cells Cellular physiology and biochemistry Medium 31502430
2024 Extracellular α-synuclein causes S1PR3 uncoupling from G protein in HeLa cells, leading to impaired retrograde trafficking of IGF-II/M6P receptor (which is under S1PR3 regulation), reduced cathepsin D lysosomal delivery, and enhanced secretion of immature pro-cathepsin D. S1PR3 G-protein coupling assay, cathepsin D activity assay, pro-cathepsin D secretion measurement, IGF-II/M6P receptor retrograde trafficking assay in HeLa cells Genes to cells Medium 38163647
2022 S1PR3 promotes aerobic glycolysis in septic macrophages via HIF-1α, HK2, and PFKFB3; S1PR3 knockdown dampens glycolysis-associated markers, retrieves LPS-modulated M1/M2 polarization balance, and attenuates NF-κB p65 activation. S1PR3 siRNA, glycolytic flux assay, macrophage polarization markers, NF-κB p65 activation, LPS-induced sepsis mouse model Biochimica et biophysica acta. Molecular cell research Medium 39549732
2025 S1PR3 activates STAT3 via a Gαi/PKA-mediated Src activation pathway in keratinocytes; activated STAT3 in turn directly upregulates S1PR3 expression forming a positive feedback loop; S1PR3 genetic deletion or pharmacological inhibition attenuates psoriasis-like skin inflammation in mice. Genetic S1pr3 deletion, S1PR3 pharmacological inhibition, Src/STAT3 phosphorylation assays, Gαi/PKA pathway dissection, STAT3 ChIP on S1PR3 promoter, skin inflammation mouse model Cell death & disease Medium 39833165
2025 S1PR3 regulates hippocampal synaptic plasticity and depression-like behavior via downregulation of RhoA/ROCK1; AAV-mediated S1PR3 overexpression in hippocampal neurons alleviates CUMS-induced depressive behavior and synaptic deficits, and these effects are normalized by RhoA expression, placing RhoA/ROCK1 downstream of S1PR3. AAV-mediated S1PR3 overexpression in hippocampal neurons, RhoA rescue experiment, behavioral tests (SPT, FST, OFT), synaptic spine density analysis, electron microscopy of synaptic ultrastructure Progress in neuro-psychopharmacology & biological psychiatry Medium 39828081
2023 CEACAM1-long isoform in neutrophils regulates susceptibility to NET formation by controlling the S1P/S1PR2/S1PR3 axis via autophagy signaling; CC1-L ablation aggravated hepatic IRI by promoting NETs in a mouse liver transplant model. Conditional knockout mouse model (CC1-L), NETosis assay, autophagy signaling assays, S1PR2/S1PR3 pathway analysis in mouse and human OLT samples The Journal of clinical investigation Medium 36719377
2023 ApoM-bound S1P shows a tendency to induce prolonged activation of Akt via S1PR1 and S1PR3 compared to albumin- or ApoA4-bound S1P, correlating with greater S1P stability and more efficient S1P release from endothelial cells. S1P stability assay, S1P release from endothelial cells, Akt phosphorylation kinetics with different S1P carrier proteins and receptor comparisons Journal of biochemistry Low 37098187

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the G(i), G(q), and G(12) families of heterotrimeric G proteins. The Journal of biological chemistry 289 10488065
2000 Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3. Molecular and cellular biology 275 11094076
2001 Sphingosine 1-phosphate-induced endothelial cell migration requires the expression of EDG-1 and EDG-3 receptors and Rho-dependent activation of alpha vbeta3- and beta1-containing integrins. The Journal of biological chemistry 255 11150298
1999 Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5. The Journal of biological chemistry 225 10383399
2001 Selective loss of sphingosine 1-phosphate signaling with no obvious phenotypic abnormality in mice lacking its G protein-coupled receptor, LP(B3)/EDG-3. The Journal of biological chemistry 221 11443127
2002 Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P(2)/LP(B2)/EDG-5 and S1P(3)/LP(B3)/EDG-3. The Journal of biological chemistry 211 12006579
2000 Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3. The Biochemical journal 197 10794715
2006 Estrogen transactivates EGFR via the sphingosine 1-phosphate receptor Edg-3: the role of sphingosine kinase-1. The Journal of cell biology 184 16636149
2000 Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5. The Journal of biological chemistry 179 10617617
1999 EDG3 is a functional receptor specific for sphingosine 1-phosphate and sphingosylphosphorylcholine with signaling characteristics distinct from EDG1 and AGR16. Biochemical and biophysical research communications 142 10381367
2014 Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation. Nature communications 131 25254944
2018 S1P/S1PR3 axis promotes aerobic glycolysis by YAP/c-MYC/PGAM1 axis in osteosarcoma. EBioMedicine 106 30587459
2003 Induction of pro-angiogenic signaling by a synthetic peptide derived from the second intracellular loop of S1P3 (EDG3). Blood 82 12763936
2002 Development of novel EDG3 antagonists using a 3D database search and their structure-activity relationships. Journal of medicinal chemistry 77 12361389
2000 Evidence for Edg-3 receptor-mediated activation of I(K.ACh) by sphingosine-1-phosphate in human atrial cardiomyocytes. Molecular pharmacology 76 10908314
2018 Sphingosine-1-phosphate promotes the proliferation and attenuates apoptosis of Endothelial progenitor cells via S1PR1/S1PR3/PI3K/Akt pathway. Cell biology international 71 29790626
2001 Sphingosine 1-phosphate activates nuclear factor-kappa B through Edg receptors. Activation through Edg-3 and Edg-5, but not Edg-1, in human embryonic kidney 293 cells. The Journal of biological chemistry 69 11673450
2001 Involvement of phospholipase D in sphingosine 1-phosphate-induced activation of phosphatidylinositol 3-kinase and Akt in Chinese hamster ovary cells overexpressing EDG3. The Journal of biological chemistry 68 11468290
2021 EGR2-mediated regulation of m6A reader IGF2BP proteins drive RCC tumorigenesis and metastasis via enhancing S1PR3 mRNA stabilization. Cell death & disease 65 34326314
2018 S1PR3 Mediates Itch and Pain via Distinct TRP Channel-Dependent Pathways. The Journal of neuroscience : the official journal of the Society for Neuroscience 56 30082422
2016 Benzyl butyl phthalate promotes breast cancer stem cell expansion via SPHK1/S1P/S1PR3 signaling. Oncotarget 56 27129165
2017 miR-127 enhances myogenic cell differentiation by targeting S1PR3. Cell death & disease 51 28358363
2017 S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis. American journal of respiratory and critical care medicine 51 28850247
2015 The G protein-coupled receptor P2RY8 and follicular dendritic cells promote germinal center confinement of B cells, whereas S1PR3 can contribute to their dissemination. The Journal of experimental medicine 50 26573295
1999 Activation of phospholipase C-Ca2+ system by sphingosine 1-phosphate in CHO cells transfected with Edg-3, a putative lipid receptor. FEBS letters 50 9928946
2018 Triple Negative Breast Cancer Depends on Sphingosine Kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P)/Sphingosine 1-Phosphate Receptor 3 (S1PR3)/Notch Signaling for Metastasis. Medical science monitor : international medical journal of experimental and clinical research 48 29605826
2023 Neutrophil CEACAM1 determines susceptibility to NETosis by regulating the S1PR2/S1PR3 axis in liver transplantation. The Journal of clinical investigation 42 36719377
2018 S1PR3 is essential for phosphorylated fingolimod to protect astrocytes against oxygen-glucose deprivation-induced neuroinflammation via inhibiting TLR2/4-NFκB signalling. Journal of cellular and molecular medicine 41 29536648
2021 Endogenous agonist-bound S1PR3 structure reveals determinants of G protein-subtype bias. Science advances 38 34108205
2002 Sphingosine 1-phosphate evokes calcium signals in C2C12 myoblasts via Edg3 and Edg5 receptors. The Biochemical journal 38 11853542
2021 The lncRNA H19/miR-766-3p/S1PR3 Axis Contributes to the Hyperproliferation of Keratinocytes and Skin Inflammation in Psoriasis via the AKT/mTOR Pathway. Mediators of inflammation 32 34992498
2003 Biochemical regulation of breast cancer cell expression of S1P2 (Edg-5) and S1P3 (Edg-3) G protein-coupled receptors for sphingosine 1-phosphate. Journal of cellular biochemistry 30 12577307
2019 S1PR3 deficiency alleviates radiation-induced pulmonary fibrosis through the regulation of epithelial-mesenchymal transition by targeting miR-495-3p. Journal of cellular physiology 29 31489649
2020 S1P lyase inhibition protects against sepsis by promoting disease tolerance via the S1P/S1PR3 axis. EBioMedicine 28 32711251
2019 Sphingosine-1-phosphate activates mouse vagal airway afferent C-fibres via S1PR3 receptors. The Journal of physiology 27 30793318
2006 Modulation of total Akt kinase by increased expression of a single isoform: requirement of the sphingosine-1-phosphate receptor, Edg3/S1P3, for the VEGF-dependent expression of Akt3 in primary endothelial cells. Experimental cell research 26 16527273
1998 Downregulation of mRNA expression of Edg-3, a putative sphingosine 1-phosphate receptor coupled to Ca2+ signaling, during differentiation of HL-60 leukemia cells. Biochemical and biophysical research communications 26 9878524
2022 S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction. Adipocyte 25 35094654
2018 S1P/S1PR3 signaling mediated proliferation of pericytes via Ras/pERK pathway and CAY10444 had beneficial effects on spinal cord injury. Biochemical and biophysical research communications 23 29534963
2022 S1PR3, as a Core Protein Related to Ischemic Stroke, is Involved in the Regulation of Blood-Brain Barrier Damage. Frontiers in pharmacology 18 35685645
2023 S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma. Journal of experimental & clinical cancer research : CR 17 36600310
2024 Targeting SphK1/S1PR3 axis ameliorates sepsis-induced multiple organ injury via orchestration of macrophage polarization and glycolysis. Biochimica et biophysica acta. Molecular cell research 16 39549732
2024 S1PR3 inhibition protects against LPS-induced ARDS by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation. Journal of translational medicine 15 38840216
2022 NF-κB and EGFR participate in S1PR3-mediated human renal cell carcinomas progression. Biochimica et biophysica acta. Molecular basis of disease 15 35346818
2012 Fingolimod inhibits PDGF-B-induced migration of vascular smooth muscle cell by down-regulating the S1PR1/S1PR3 pathway. Biochimie 15 22828274
2021 Hirudin, a thrombin inhibitor, attenuates TGF-β-induced fibrosis in renal proximal tubular epithelial cells by inhibition of protease-activated receptor 1 expression via S1P/S1PR2/S1PR3 signaling. Experimental and therapeutic medicine 13 34815755
2009 EDG3 and SHC3 on chromosome 9q22 are co-amplified in human ependymomas. Cancer letters 13 19748727
2022 Targeting SPHK1/S1PR3-regulated S-1-P metabolic disorder triggers autophagic cell death in pulmonary lymphangiomyomatosis (LAM). Cell death & disease 10 36543771
2018 Role of S1P/S1PR3 axis in release of CCL20 from human bronchial epithelial cells. PloS one 10 30192865
2024 SphK1 deficiency ameliorates the development of atherosclerosis by inhibiting the S1P/S1PR3/Rhoa/ROCK pathway. Cellular signalling 9 38852936
2021 S1PR3-G12-biased agonist ALESIA targets cancer metabolism and promotes glucose starvation. Cell chemical biology 9 33561428
2019 Thrombin Contributes to Anti-myeloperoxidase Antibody Positive IgG-Mediated Glomerular Endothelial Cells Activation Through SphK1-S1P-S1PR3 Signaling. Frontiers in immunology 9 30891029
2019 FTY720P Upregulates the Na+/K+ ATPase in HepG2 Cells by Activating S1PR3 and Inducing PGE2 Release. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 9 31502430
1999 Molecular cloning of EDG-3 and N-Shc genes from the puffer fish, Fugu rubripes, and conservation of synteny with the human genome. FEBS letters 9 10508926
2025 S1PR3-driven positive feedback loop sustains STAT3 activation and keratinocyte hyperproliferation in psoriasis. Cell death & disease 8 39833165
2015 Corticotrophin-releasing factor participates in S1PR3-dependent cPLA2 expression and cell motility in vascular smooth muscle cells. Vascular pharmacology 8 25869501
1997 The immediate-early gene product MAD-3/EDG-3/IkappaB alpha is an endogenous modulator of fibroblast growth factor-1 (FGF-1) dependent human endothelial cell growth. FEBS letters 8 9315732
2021 Identification of S1PR3 gene signature involved in survival of sepsis patients. BMC medical genomics 7 33549110
2020 A Novel Function of Sphingolipid Signaling via S1PR3 in Hematopoietic and Leukemic Stem Cells. Blood cancer discovery 7 34661148
2023 Sphingosine 1-Phosphate Activates S1PR3 to Induce a Proinflammatory Phenotype in Human Myometrial Cells. Endocrinology 6 37120767
2024 S1PR3 agonism and S1P lyase inhibition rescue mice in the severe state of experimental sepsis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 5 38599060
2024 Hydroxysafflor yellow A, a natural food pigment, ameliorates atherosclerosis in ApoE-/- mice by inhibiting the SphK1/S1P/S1PR3 pathway. Food science & nutrition 5 39620014
2022 Transforming Growth Factor Beta Promotes the Expansion of Cancer Stem Cells via S1PR3 by Ligand-Independent Notch Activation. Biological & pharmaceutical bulletin 5 35491169
2021 CRH/CRHR1 modulates cerebrovascular endothelial cell permeability in association with S1PR2 and S1PR3 under oxidative stress. Vascular pharmacology 5 34781017
2018 SPHK1 promotes metastasis of thyroid carcinoma through activation of the S1P/S1PR3/Notch signaling pathway. Experimental and therapeutic medicine 5 29805524
2023 MicroRNA-127 promotes anti-microbial ability in porcine alveolar macrophages via S1PR3/TLR signaling pathway. Journal of veterinary science 4 37012029
2023 S1P-S1PR3-RAS promotes the progression of S1PR3hi TAL1+ T-cell acute lymphoblastic leukemia that can be effectively inhibited by an S1PR3 antagonist. Leukemia 4 37591940
2023 Apolipoprotein M supports S1P production and conservation and mediates prolonged Akt activation via S1PR1 and S1PR3. Journal of biochemistry 3 37098187
2025 S1PR3 in hippocampal neurons improves synaptic plasticity and decreases depressive behavior via downregulation of RhoA/ROCK1. Progress in neuro-psychopharmacology & biological psychiatry 2 39828081
2025 The suppression of the SPHK1/S1P/S1PR3 signaling pathway diminishes EGFR activation and increases the sensitivity of non-small cell lung cancer to gefitinib. Current research in pharmacology and drug discovery 2 39896887
2024 S1PR3 suppresses the inflammatory response and extracellular matrix degradation in human nucleus pulposus cells. Experimental and therapeutic medicine 2 38756905
2024 Transplantation of miR-193b-3p-Transfected BMSCs Improves Neurological Impairment after Traumatic Brain Injury through S1PR3-Mediated Regulation of the PI3K/AKT/mTOR Signaling Pathway. Critical reviews in eukaryotic gene expression 2 39072405
2022 [Knockout of S1PR3 attenuates acute lung injury in mice by inhibiting the MAPK pathway]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2 36651249
2024 The Specific ROCK2 Inhibitor KD025 Alleviates Glycolysis through Modulating STAT3-, CSTA- and S1PR3-Linked Signaling in Human Trabecular Meshwork Cells. Biomedicines 1 38927372
2026 S1PR3 Inactivation Aggravates Cerebrovascular Endothelial Cell Permeability Mediated by cPLA2 and STAT3 Phosphorylation Under Oxidative Stress. Basic & clinical pharmacology & toxicology 0 41623209
2026 S1PR3 antagonism ameliorates endothelial dysfunction in septic acute kidney injury through the ROCK1-Drp1 signalling pathway. Molecular immunology 0 41691873
2026 S1P/S1PR3 axis drives epithelial dysfunction and type 2 inflammation in chronic rhinosinusitis with nasal polyps. Mucosal immunology 0 41806939
2026 S1PR3 expression independently predicts the cumulative incidence of relapse in adult B-cell acute lymphoblastic leukemia: a single-center retrospective analysis. American journal of clinical pathology 0 42001307
2025 S1PR3 inhibition impairs cell cycle checkpoint via the AKT/WEE1 pathway in oral squamous cell carcinoma. Journal of translational medicine 0 40410851
2025 Integrated systems biology approach reveals the potential mechanism of Guanxinning in treating coronary heart disease complicated with major depressive disorder through S1PR3 regulation. Computers in biology and medicine 0 40472508
2025 Effects of sphingolipid metabolism related genes-SPTLC1, ORMDL3, SPHK1 and S1PR3 polymorphisms on susceptibility to hashimoto's thyroiditis. Journal of endocrinological investigation 0 40782218
2025 TET1-Mediated DNA hydroxymethylation of KLF6 promotes LPS-induced pulmonary fibrosis by activating the S1PR3/RhoA/ROCK signaling pathway. Respiratory research 0 41316224
2025 S1PR3 Inhibition in alveolar epithelial cells alleviates pulmonary fibrosis by enhancing alveolar barrier function. Respiratory research 0 41387860
2025 S1PR3 mediates glial stimulated tumor invasion in response to interstitial fluid flow. bioRxiv : the preprint server for biology 0 41573902
2024 Extracellular α-synuclein impairs sphingosine 1-phosphate receptor type 3 (S1PR3)-regulated lysosomal delivery of cathepsin D in HeLa cells. Genes to cells : devoted to molecular & cellular mechanisms 0 38163647