Affinage

S1PR1

Sphingosine 1-phosphate receptor 1 · UniProt P21453

Length
382 aa
Mass
42.8 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

S1PR1 (EDG-1) is a high-affinity (~8 nM Kd) G protein-coupled receptor for sphingosine-1-phosphate that signals exclusively through the Gi family to control cell migration, vascular integrity, and lymphocyte trafficking (PMID:9488656, PMID:10488065). Its third intracellular loop binds Giα/Goα in a GTPγS-sensitive manner, and ligand engagement inhibits adenylate cyclase and drives sustained, pertussis toxin-sensitive MAP kinase activation without coupling to Gq, G12, or G13 (PMID:9660876, PMID:8626678, PMID:10383399). A defining output is Gi-dependent activation of the small GTPase Rac, which is required for cortical actin assembly, lamellipodia formation, and chemotaxis; Rac activation additionally requires Akt-mediated phosphorylation of the receptor at T236, while cytoskeletal integration of growth factor cues (PDGF, HGF, aPC/PAR1) proceeds through S1PR1 transactivation downstream of sphingosine kinase and β-arrestin (PMID:11032855, PMID:11583630, PMID:11230698, PMID:23212923, PMID:34873055). Genetic deletion is embryonic lethal from vascular hemorrhage due to defective mural-cell coverage, and in endothelium S1PR1 stabilizes VE-cadherin junctions, restrains VEGF/VEGFR3-driven sprouting via RhoA inhibition, and activates AKT/eNOS to set vascular tone and blood pressure (PMID:11032855, PMID:22975327, PMID:32544090, PMID:28607130, PMID:31854513). In the immune system, S1PR1 senses S1P gradients to drive lymphocyte egress from thymus and lymph nodes, a function dependent on dynamin 2-mediated internalization/recycling that sustains signaling (PMID:24638168, PMID:26862175). Receptor trafficking is governed by an essential C-terminal domain, N-glycosylation at Asn30 (required for internalization and caveolae targeting), and tyrosine-143 phosphorylation; CD69 acts as a cis transmembrane protein agonist contacting TM4 to allosterically activate the receptor and drive internalization that blocks egress (PMID:10198065, PMID:12087059, PMID:25588843, PMID:37039481). S1PR1 resides in caveolin-1-enriched caveolae where caveolin-1 inhibits its signaling, and it forms a STAT3-driven positive feedback loop (via JAK2/IL-6) that sustains STAT3 activity in tumors and hypothalamic neurons (PMID:10921915, PMID:21102457, PMID:25255053). Cryo-EM structures of S1PR1-Gi complexes define agonist binding modes and the activation switch (PMID:34526663).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    Established that the orphan receptor EDG-1 engages inhibitory G proteins through a defined cytosolic interface, providing the first mechanistic link to a signaling output.

    Evidence Co-IP and GTPγS competition mapping i3 loop association with Giα/Goα plus pertussis toxin-sensitive MAPK assays

    PMID:8626678

    Open questions at the time
    • Endogenous ligand not yet known at this point
    • No structural detail of coupling
  2. 1998 High

    Identified S1P as the high-affinity physiological ligand and showed receptor engagement drives Gi-restricted cAMP inhibition and Rho-dependent morphogenesis, defining EDG-1 as the S1P receptor.

    Evidence Radioligand binding (Kd ~8 nM), heterologous expression with cAMP/MAPK assays, pertussis toxin dissection

    PMID:9480864 PMID:9488656 PMID:9660876 PMID:9705355

    Open questions at the time
    • LPA acts only as a low-affinity agonist; physiological relevance unclear
    • Selectivity among Gi members not yet resolved
  3. 1999 High

    Resolved that S1PR1 couples exclusively to Gi (not Gq/G12/G13), distinguishing it from sibling S1P receptors and explaining its calcium-silent, migration-centric signaling.

    Evidence Subunit-selective [35S]GTPγS binding in Sf9/HEK293 and Xenopus oocyte chimeric Gαqi complementation

    PMID:10383399 PMID:10488065

    Open questions at the time
    • Downstream effectors of Gi not fully enumerated
    • Does not address receptor trafficking
  4. 2000 High

    Demonstrated S1PR1 is essential for vascular maturation in vivo and links receptor activity to Rac-dependent migration, defining its developmental role.

    Evidence Edg1-/- mouse knockout with vascular histology and Rac activation assays; caveolae fractionation showing caveolin-1 interaction

    PMID:10921915 PMID:11032855

    Open questions at the time
    • Cell-type-specific contributions not separated
    • How caveolin-1 inhibits signaling mechanistically unresolved
  5. 2001 High

    Defined Akt phosphorylation at T236 as a switch enabling Rac activation and chemotaxis, and established S1PR1 as the obligatory transactivation node for PDGF-driven cytoskeletal remodeling.

    Evidence Site-directed mutagenesis (T236A dominant-negative), Akt-receptor binding, β-arrestin translocation, EDG-1-null fibroblast chemotaxis and FAK/Src/p38 assays

    PMID:11150298 PMID:11230698 PMID:11557736 PMID:11583630 PMID:11726541

    Open questions at the time
    • Whether T236 phosphorylation is direct in vivo across cell types
    • Integration of Rho vs Rac outputs context-dependent
  6. 2002 High

    Mapped receptor trafficking determinants — C-terminus and Asn30 N-glycosylation — required for ligand-induced internalization and caveolae targeting.

    Evidence GFP-chimera live imaging, C-terminal truncation, N30D glycosylation mutant with binding/MAPK/internalization assays

    PMID:10198065 PMID:12087059

    Open questions at the time
    • Specific endocytic adaptors not identified at this stage
    • Functional consequence of recycling for signaling not yet defined
  7. 2010 High

    Revealed a STAT3–S1PR1 positive feedback loop that sustains persistent STAT3 activity, linking the receptor to tumor growth and metastasis.

    Evidence S1PR1 siRNA, STAT3 reporter, JAK2 kinase activity, IL-6 ELISA and in vivo tumor models

    PMID:21102457

    Open questions at the time
    • Whether S1PR1-STAT3 coupling is direct or indirect via JAK2/IL-6
    • Generality across tumor types
  8. 2012 High

    Established endothelial S1PR1 as a brake on sprouting angiogenesis through VE-cadherin stabilization and VEGF antagonism, and showed it directs proplatelet shedding in megakaryocytes.

    Evidence Endothelial and megakaryocyte conditional S1pr1 deletion, VE-cadherin imaging, intravital bone marrow microscopy; c-Met/ITGB4 co-IP transactivation

    PMID:22975327 PMID:23148237 PMID:23212923

    Open questions at the time
    • Quantitative balance between S1PR1 quiescence and VEGF sprouting cues unclear
    • Tissue-specific signaling differences not unified
  9. 2015 High

    Identified tyrosine-143 phosphorylation as the controller of internalization-recycling cycling in endothelial cells.

    Evidence Y143F/Y143D mutagenesis with flow cytometry internalization and barrier resistance assays

    PMID:25588843

    Open questions at the time
    • Kinase responsible for Y143 phosphorylation unidentified
    • Relationship between Y143 and C-terminal serine phosphorylation
  10. 2016 High

    Showed that sustained S1PR1 signaling via dynamin 2-dependent internalization/recycling is the mechanistic basis for lymphocyte egress and that the receptor suppresses type I IFN amplification in pDCs.

    Evidence Dynamin 2 conditional KO with S1PR1 transgenic rescue, inducible T cell S1PR1 KO with intravital imaging, Tat-peptide internalization blockade and IFNAR1 turnover assays

    PMID:22334704 PMID:24638168 PMID:26787880 PMID:26862175 PMID:30877143

    Open questions at the time
    • Precise signal duration required for egress not quantified
    • How CCR7 and S1PR1 signals are integrated at sinus entry
  11. 2017 High

    Connected endothelial S1PR1/eNOS signaling to blood pressure control and tissue repair, and revealed pro-tumor inflammasome signaling in macrophages.

    Evidence Endothelial-specific KO with eNOS/blood pressure measurement, FTY720 pharmacology, macrophage-specific S1pr1 KO with NLRP3/IL-1β and lymphangiogenesis readouts, ERK/CSF1 epistasis

    PMID:28607130 PMID:28739604 PMID:30877143 PMID:32091582

    Open questions at the time
    • Cell-context determinants of pro- vs anti-tumor outcomes unresolved
    • Mechanism linking Gi to eNOS not fully detailed
  12. 2021 High

    Provided atomic-resolution structures of S1PR1-Gi complexes defining agonist binding and activation, and dissected an aPC/PAR1-β-arrestin2-SphK1-S1PR1-Akt survival axis and an anti-apoptotic JNK/BCL2 role.

    Evidence Cryo-EM of S1PR1-Gi with multiple agonists; endothelial siRNA epistasis for the aPC/PAR1 axis; receptor internalization-deficient mouse mutants with JNK/BCL2 and patient validation

    PMID:34526663 PMID:34873055 PMID:38194271

    Open questions at the time
    • Structural basis of biased/β-arrestin signaling not captured
    • How internalization residues couple to JNK restraint mechanistically
  13. 2023 High

    Solved the structural and functional basis for CD69 acting as a cis transmembrane protein agonist that drives S1PR1 internalization to block egress, and confirmed direct S1PR1-STAT3 binding in carcinoma.

    Evidence Cryo-EM of CD69-S1PR1-Gi with interface mutagenesis, internalization and egress assays; S1PR1-STAT3 co-IP with KD/OE tumor assays; zebrafish s1pr1 loss in astrocytes

    PMID:31438989 PMID:37039481 PMID:38096817

    Open questions at the time
    • Whether STAT3 binding is truly direct rests on single co-IP studies
    • CNS/glial roles characterized only in non-mammalian models

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple transcriptional inputs (STAT1, STAT3, KLF2, SMYD3/H3K4me3) and post-translational modifications are integrated to set S1PR1 surface density and signaling output in a given cell type remains unresolved.
  • No unified model of receptor abundance control across tissues
  • Kinases for individual phosphosites incompletely identified
  • Biased signaling between Gi and β-arrestin arms not structurally defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0008289 lipid binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 3
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-109582 Hemostasis 1
Partners
AKT1CAV1CD69GNAI1GNAI3ITGB4METSTAT3

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Sphingosine-1-phosphate (S1P/SPP) was identified as a high-affinity ligand for the orphan GPCR EDG-1 (S1PR1), binding with Kd ~8.1 nM; receptor overexpression induced cell-cell aggregation, cadherin upregulation, and adherens junction formation in an S1P- and Rho-dependent manner. Radioligand binding assay, receptor overexpression in HEK293 cells, morphological and biochemical assays Science High 9488656
1998 EDG-1 (S1PR1) couples exclusively to the Gi pathway: binding of S1P to EDG-1 inhibits forskolin-stimulated cAMP accumulation in a pertussis toxin-sensitive manner; S1P-induced mitogenesis and anti-apoptosis were independent of EDG-1 and correlated with intracellular S1P uptake. cAMP assay with pertussis toxin inhibition, intracellular microinjection of S1P, antisense and receptor expression studies The Journal of cell biology High 9660876
1996 The third cytosolic loop (i3) of EDG-1 (S1PR1) physically associates with Giα and Goα polypeptides in a GTPγS-sensitive manner; immunoprecipitation of EDG-1 co-precipitates Giα1 and Giα3; EDG-1 overexpression leads to sustained, pertussis toxin-sensitive MAP kinase activation. Co-immunoprecipitation, GTPγS competition assay, MAP kinase activity assay with pertussis toxin The Journal of biological chemistry High 8626678
1999 EDG-1 (S1PR1) activates only Gi family members (not Gs, Gq, G12, or G13), as established by subunit-selective [35S]GTPγS binding in Sf9 and HEK293 cells; in contrast, EDG-3 and H218/EDG-5 additionally couple to Gq and G13. Subunit-selective [35S]GTPγS binding assay in Sf9 and HEK293 cells The Journal of biological chemistry High 10488065
1999 S1P ligand binding specifically induces reversible trafficking of EDG-1 (S1PR1) from the plasma membrane to perinuclear endosomal/lysosomal vesicles (t1/2 ~15 min internalization, t1/2 ~30 min recycling); truncation of the C-terminus completely blocks internalization; C-terminal domain is essential for ligand-induced trafficking. EDG-1-GFP chimera live-cell imaging, subcellular colocalization with endocytic/lysosomal markers, C-terminal truncation mutant analysis Molecular biology of the cell High 10198065
2000 Genetic deletion of Edg-1 (S1PR1) in mice caused embryonic hemorrhage and death at E12.5–E14.5 due to deficient vascular smooth muscle cell/pericyte coverage; EDG-1-null cells failed to activate the small GTPase Rac in response to S1P, which is required for migration. Gene knockout in mice (Edg1−/− embryos), histology, Rac activation assay in mutant cells The Journal of clinical investigation High 11032855
2001 S1P-induced endothelial cell migration requires Akt-mediated phosphorylation of EDG-1 (S1PR1) at the T236 residue in the third intracellular loop; activated Akt binds to EDG-1, and T236A mutant EDG-1 acts as a dominant-negative that sequesters Akt and blocks Rac activation, cortical actin assembly, and chemotaxis without affecting Gi-dependent signaling. Akt-EDG-1 binding assay, site-directed mutagenesis (T236A), in vitro migration/chemotaxis assay, Rac activation assay, dominant-negative analysis Molecular cell High 11583630
2001 PDGF-induced cell motility depends on EDG-1 (S1PR1): PDGF activates sphingosine kinase, raising intracellular S1P levels, which transactivates EDG-1 as demonstrated by β-arrestin translocation and EDG-1 phosphorylation; EDG-1-null or kinase-inhibited cells fail to activate Rac or migrate toward PDGF. EDG-1 knockout fibroblasts, β-arrestin translocation assay (GPCR transactivation), sphingosine kinase inhibition, chemotaxis assay, Rac activation Science High 11230698
2001 SPP-induced HUVEC migration requires signaling via EDG-1 and EDG-3 receptors through Rho activation (blocked by C3 exotoxin), leading to Rho-dependent integrin clustering (αvβ3 and β1) into focal contacts; Rac activation was dispensable for adhesion but EDG-1 and EDG-3 were both required for Rho activation. Antisense oligonucleotide knockdown of EDG-1 and EDG-3, C3 exotoxin treatment, integrin blocking antibodies, Rho activation assay, cell adhesion/migration assay The Journal of biological chemistry High 11150298
2000 EDG-1 (S1PR1) localizes to caveolin-1-enriched plasmalemmal caveolae (~55% of protein); co-immunoprecipitation shows direct EDG-1/caveolin-1 interaction; S1P treatment increases EDG-1 targeting to caveolae (~93%); caveolin-1 overexpression inhibits S1P-mediated eNOS activation and attenuates agonist-induced EDG-1 phosphorylation by >90%. Sucrose gradient ultracentrifugation fractionation, co-immunoprecipitation with anti-caveolin-1 antibody, eNOS activity assay, caveolin-1 overexpression The Journal of biological chemistry High 10921915
2001 EDG-1 (S1PR1) expression in vascular smooth muscle cells (VSMCs) enhances S1P-induced proliferation via Gi-dependent p70 S6 kinase activation and cyclin D1 expression (blocked by pertussis toxin and rapamycin), and enhances migration via Gi activation but independently of p70 S6 kinase. Stable transfection of EDG-1 into adult VSMCs, pertussis toxin treatment, rapamycin treatment, p70 S6 kinase assay, cyclin D1 western blot, migration assay Circulation research High 11557736
1999 EDG-1 (S1PR1) couples to Gi but not Gq: EDG-1 mRNA expression in Xenopus oocytes did not confer S1P-responsive intracellular calcium transients unless co-expressed with the chimeric Gαqi protein; in contrast, EDG-3 and EDG-5 alone conferred calcium responses to S1P, demonstrating differential Gq/Gi coupling among S1P receptors. Xenopus oocyte expression system, microinjection of receptor mRNA ± chimeric G-protein constructs, electrophysiological calcium transient recording The Journal of biological chemistry High 10383399
2002 EDG-1 (S1PR1) is N-glycosylated at asparagine-30 in its extracellular N-terminus; non-glycosylated mutant N30D-Edg-1 shows normal plasma membrane expression, ligand binding, and MAP kinase activation, but markedly reduced ligand-induced internalization and is not associated with caveolae membrane fractions. Site-directed mutagenesis (N30D), sucrose density gradient fractionation, radioligand binding assay, MAP kinase assay, internalization assay FASEB journal High 12087059
2010 STAT3 transcriptionally drives S1PR1 expression; reciprocally, S1PR1 activates STAT3 by upregulating JAK2 tyrosine kinase activity and IL-6 gene expression, forming a positive feedback loop that sustains persistent STAT3 activation in cancer cells; silencing S1PR1 inhibits STAT3 activity, tumor growth, and metastasis. S1PR1 siRNA knockdown in tumor/immune cells, STAT3 reporter assay, JAK2 kinase activity measurement, IL-6 ELISA, in vivo tumor models Nature medicine High 21102457
2012 S1PR1 signaling restricts sprouting angiogenesis by inhibiting VEGF-A-induced signaling and stabilizing VE-cadherin localization at endothelial junctions; loss of S1PR1 in endothelial cells leads to increased sprouting and ectopic vessel branching. S1PR1 loss-of-function in endothelial cells (genetic deletion), VE-cadherin localization by immunofluorescence, VEGF-A signaling assays Developmental cell High 22975327
2012 S1PR1 (S1pr1) on megakaryocytes functions as a directional cue receptor for S1P gradients, guiding proplatelet extensions into bone marrow sinusoids; conditional S1pr1 deletion causes severe thrombocytopenia due to aberrant extravascular proplatelet formation and defective intravascular shedding. Conditional mouse mutants, intravital multiphoton microscopy of bone marrow, platelet counts The Journal of experimental medicine High 23148237
2001 S1P activates NF-κB in a receptor-dependent fashion through EDG-3 and EDG-5 (which couple to Gi, Gq, and G13), but not through EDG-1 (S1PR1, which couples to Gi only); NF-κB activation requires protein kinase C and Ca2+ downstream of Gq; Rho activation alone by S1P was insufficient for NF-κB activation. HEK293 cells overexpressing individual Edg receptors, NF-κB reporter assay, PKC and Ca2+ inhibitor studies The Journal of biological chemistry High 11673450
2014 Dynamin 2-dependent endocytosis is required for sustained S1PR1 signaling and T cell egress: in low S1P concentrations, dynamin 2 enables S1PR1 internalization/recycling which sustains signaling sufficient for egress; dynamin 2 deficiency limits T cells to a single pulse of S1PR1 signaling, insufficient for egress; transgenic S1PR1 overexpression rescues egress in dynamin 2 KO mice. T cell-specific dynamin 2 conditional KO mouse, S1PR1 transgenic rescue, T cell egress assay from thymus and lymph nodes The Journal of experimental medicine High 24638168
2016 S1PR1 signaling suppresses the type I IFN autoamplification loop in plasmacytoid dendritic cells by accelerating IFNAR1 turnover/degradation and downregulating STAT1 phosphorylation; this suppression is pertussis toxin-resistant and requires S1PR1 internalization (blocked by a C-terminal Tat-peptide); endogenous S1P-S1PR1 signaling sets pDC sensitivity for IFN-α amplification. S1PR1 agonist treatment of pDCs, Tat-fusion receptor internalization blocking peptide, IFNAR1 turnover measurement, STAT1 phosphorylation assay, in vivo Ex26 antagonist, pertussis toxin studies Proceedings of the National Academy of Sciences of the United States of America High 26787880
2021 Cryo-EM structures of S1PR1 and S1PR5 in complex with heterotrimeric Gi protein and diverse agonists (including drugs) were determined; structures reveal the binding modes of chemically distinct agonists, a mechanical switch activating the receptors, and the basis for ligand selectivity and G-protein coupling. Cryo-electron microscopy structure determination, functional assays for ligand activation and G-protein coupling Cell research High 34526663
2023 CD69, a transmembrane protein expressed on activated lymphocytes, acts as a protein agonist of S1PR1 in cis: cryo-EM structure shows the transmembrane helix of one CD69 homodimer protomer contacts S1PR1-TM4, allosterically inducing movement of S1PR1-TMs 5-6 to activate receptor and engage heterotrimeric Gi; mutations at the CD69-S1PR1 interface reduce receptor internalization; CD69 promotes Gi-dependent S1PR1 internalization, loss of S1P gradient sensing, and inhibition of lymphocyte egress. Cryo-EM structure of CD69-S1PR1-Gi complex, mutagenesis of interface residues, receptor internalization assay, lymphocyte egress assay eLife High 37039481
2015 Phosphorylation of S1PR1 at tyrosine-143 (Y143) is required for S1P-induced receptor internalization in endothelial cells; Y143 phosphorylation correlates with maximal receptor internalization at 20 min and Y143 dephosphorylation accompanies receptor recycling to the cell surface at ~1 h; phospho-defective Y143F mutant fails to internalize while phospho-mimicking Y143D shows constitutive high internalization; C-terminal serine phosphorylation did not modulate Y143-dependent internalization. Site-directed mutagenesis (Y143F, Y143D), flow cytometry/immunofluorescence internalization assay, endothelial barrier resistance measurement Journal of cell science High 25588843
1998 Edg-1 (S1PR1) expression in Sf9 and COS-7 cells confers S1P-induced adenylate cyclase inhibition and MAP kinase activation (Gi-mediated), but not Ca2+ mobilization; LPA does not activate EDG-1 and Vzg-1/Edg-2 cannot substitute for Edg-1. Heterologous expression in Sf9 and COS-7 cells, adenylate cyclase assay, MAP kinase assay The Biochemical journal High 9480864
2017 S1PR1 signaling in endothelial cells activates the ERK/CSF1 pathway, enhancing CSF1 expression in a cell-contact-dependent manner, which promotes Ly6clow reparative macrophage proliferation after myocardial infarction; endothelial S1pr1-specific deletion reduces reparative macrophage accumulation and worsens cardiac remodeling; pharmacological S1pr1 activation ameliorates post-MI cardiac remodeling. Endothelial-specific S1pr1 KO mouse model, pharmacological S1pr1 activation, flow cytometry for macrophage subsets, CSF1 signaling blockade, ERK activation assay Cardiovascular research High 32091582
2016 In T lymphocytes, CCR7/CCL19 signaling upregulates S1PR1 (EDG-1) expression via ERK5 activation and induction of the KLF2 transcription factor; CCR7/CCL19-stimulated T cells show increased S1PR1-ligand-directed migration at 48 h, which is abolished in ERK5-deficient T cells. ERK5 conditional KO mouse (ERK5flox/flox/Lck-Cre), primary murine T cell stimulation, migration assay to S1PR1 ligands, KLF2 and S1PR1 expression analysis The Journal of biological chemistry Medium 22334704
2004 S1P1 (S1PR1) signaling in the developing vasculature regulates limb development non-cell-autonomously: loss of S1P1 in endothelium causes HIF-1α and VEGF induction in limbs (but not in embryonic fibroblasts), leading to hyperplastic vasculature and defective digit/chondrocyte morphogenesis; endothelium-specific S1P1 null mice recapitulate limb defects. Whole-body and endothelium-specific S1p1 KO mice, HIF-1α/VEGF immunostaining, limb histology Developmental biology High 15063179
2016 T cell-intrinsic S1PR1 is required for effector T cell entry into lymphatic sinuses and egress from draining lymph nodes during infection; using inducible T cell-specific S1PR1 KO, WT and S1PR1-deficient effector T cells both migrate to sinus-adjacent positions but only WT T cells enter sinuses, even when CCR7 retention signals are downregulated. Inducible T cell-specific S1PR1 gene deletion, intravital two-photon microscopy of lymph node, viral infection model Proceedings of the National Academy of Sciences of the United States of America High 26862175
2019 CD4 T cell S1PR1 and S1PR4, and endothelial cell S1PR2, are each required for T cell migration across lymphatic endothelial cells (LECs) and into afferent lymphatic vessels and draining lymph nodes; S1PR1 and S1PR4 differentially regulate T cell motility and VCAM-1 binding; S1PR2 in LECs regulates VE-cadherin, occludin, and zonulin-1 expression via ERK. Receptor-specific KO and blockade, transwell migration assay across LECs, intravital imaging, VCAM-1 binding assay, VE-cadherin/occludin/ZO-1 immunostaining Science immunology High 30877143
2012 HGF activates S1PR1 transactivation via c-Met: c-Met, S1PR1, and integrin β4 (ITGB4) are recruited to caveolin-enriched lipid rafts upon HGF treatment; co-immunoprecipitation shows direct c-Met interaction with both S1PR1 and ITGB4; S1PR1 siRNA attenuates ITGB4 and Rac1 activation, c-Met/ITGB4 interaction, and transendothelial electrical resistance. Co-immunoprecipitation, lipid raft fractionation, siRNA knockdown of S1PR1 and ITGB4, Rac1 activation assay, transendothelial electrical resistance measurement The Journal of biological chemistry High 23212923
2016 S1PR1 regulates lymphatic vascular quiescence by antagonizing laminar shear stress (LSS)-mediated VEGF-C/VEGFR3 signaling; S1PR1 inhibits RhoA activity to promote membrane localization of claudin-5 (tight junction molecule); S1pr1 loss in LECs induces hypersprouting rescued by reducing Vegfr3 gene dosage in vivo. LEC-specific S1pr1 KO, Vegfr3 heterozygous rescue genetics, in vitro LSS experiments, RhoA activation assay, claudin-5 membrane localization JCI insight High 32544090
2017 S1PR1 signaling in tumor-associated macrophages (TAMs) promotes lymphangiogenesis and pulmonary metastasis via NLRP3 inflammasome activation and IL-1β production; macrophage-specific S1pr1 deletion reduces Nlrp3 expression in TAMs and prevents tumor lymphangiogenesis and metastasis; macrophage-dependent lymphangiogenesis in vitro requires both S1PR1 signaling and IL-1β production. CD11b+ macrophage-specific S1pr1 KO mouse, transcriptome analysis of isolated TAMs, in vitro lymphangiogenesis assay, inflammasome activation The Journal of experimental medicine High 28739604
2021 S1PR1 limits apoptosis in T cells by maintaining BCL2 family member balance via restraint of JNK activity; the same intracellular residues enabling S1PR1 internalization are required to prevent the proapoptotic cascade; this is distinct from S1PR1's role in directing egress. Mouse genetic models (S1PR1 internalization-deficient mutants), JNK activity assay, BCL2 family member expression, T cell survival assay; findings confirmed in ozanimod-treated ulcerative colitis patients The Journal of clinical investigation High 38194271
2013 β1-adrenergic receptor (β1AR) and S1PR1 physically interact and show reciprocal cross-regulation: S1PR1 agonist (S1P) can induce β1AR downregulation, and β-AR agonist (isoproterenol) can induce S1PR1 downregulation; G-protein-coupled receptor kinase-2 (GRK2) is involved; this cross-talk is observed in mouse hearts under chronic β-AR stimulation and in a rat heart failure model. HEK293 cells overexpressing both receptors, receptor downregulation assays, co-immunoprecipitation, in vivo mouse cardiac model, rat heart failure model Circulation Medium 23969695
1998 Lysophosphatidic acid (LPA) is a low-affinity agonist for EDG-1 (S1PR1): LPA binds with Kd ~2.3 μM (vs ~8 nM for S1P), induces receptor phosphorylation, MAP kinase activation, and Rho-dependent morphogenesis. Radioligand binding assay, receptor phosphorylation assay, MAP kinase assay, morphological analysis The Journal of biological chemistry High 9705355
2001 PDGF-induced focal adhesion formation and activation of FAK, Src, and p38 are dysregulated in EDG-1-null fibroblasts; PDGF-induced lamellipodia extension and cell motility are abrogated in EDG-1-null cells; in contrast, mitogenesis, survival responses, and ERK1/2 activation by PDGF or S1P are unaffected by EDG-1 deletion, indicating EDG-1 is required for cytoskeletal integration but not growth signals. EDG-1-null fibroblasts, FAK/Src/p38 kinase activation assays, lamellipodia observation, cell motility assay FASEB journal High 11726541
2016 miR302-367 elevation in endothelial cells promotes vascular stability and reduces sprouting angiogenesis via an Erk1/2-Klf2-S1pr1 pathway: downregulation of Erk1/2 increases Klf2, which induces S1pr1 and its target VE-cadherin; pharmacological blockade or genetic deletion of S1pr1 in ECs reverses the antiangiogenic effect of miR302-367. miRNA overexpression in ECs, retinal vascular assay, endothelial-specific S1pr1 deletion, ERK/KLF2/S1PR1/VE-cadherin expression and function assays Circulation research High 27756792
2017 S1PR1 signaling in endothelial cells controls blood pressure and flow-mediated mechanotransduction: endothelial-specific S1PR1 deletion decreases basal and stimulated eNOS-derived nitric oxide and elevates baseline blood pressure; FTY720 (functional S1PR1 antagonist) markedly decreases endothelial S1PR1, increases blood pressure in control mice, and exacerbates angiotensin II-induced hypertension. Endothelial-specific S1PR1 KO mice, eNOS activity assay, blood pressure measurement, FTY720 pharmacological treatment, angiotensin II hypertension model Hypertension High 28607130
2016 S1P in HDL promotes physical interaction between SR-BI and S1PR1 on the plasma membrane; HDL-derived S1P initiates S1PR1 internalization and intracellular calcium flux; HDL without supplemented S1P did not trigger these responses, establishing S1P as the active component mediating HDL-induced S1PR1 activation and SR-BI/S1PR1 interaction. Protein-fragment complementation assay (SR-BI/S1PR1 interaction), confocal microscopy, calcium flux assay, recombinant HDL particles ± S1P, primary vascular smooth muscle cells and HEK293 cells Journal of lipid research Medium 27881715
2021 aPC/PAR1 anti-apoptotic signaling is mediated by a discrete β-arrestin-2-SphK1-S1PR1-Akt axis in endothelial cells: aPC activates PAR1 to engage β-arr2, which activates SphK1 independent of Dvl2, leading to S1PR1 transactivation and Akt-dependent cell survival; endogenous PAR1 and S1PR1 co-reside in caveolin-1-rich microdomains, and Cav1 is required for this pathway. Endothelial cell siRNA knockdown of β-arr2, SphK1, S1PR1, Cav1; co-immunoprecipitation; Akt phosphorylation; cell apoptosis assay Proceedings of the National Academy of Sciences of the United States of America High 34873055
2014 S1P/S1PR1 signaling in hypothalamic POMC neurons activates STAT3 and the melanocortin system to reduce food intake and increase energy expenditure; STAT3 controls S1PR1 expression in neurons via a positive feedback; selective disruption of hypothalamic S1PR1 increases food intake and reduces respiratory exchange ratio. Intracerebroventricular S1P injection, hypothalamic S1PR1-selective disruption in rodents, STAT3 activity assay, food intake and energy expenditure measurements Nature communications High 25255053
2020 STAT1 transcriptionally regulates S1PR1 expression by binding its promoter in the region -29 to -12 bp upstream of TSS; STAT1 knockdown reduces S1PR1 expression, STAT1 overexpression upregulates it, and IFN-γ activation of STAT1 increases S1PR1 mRNA and protein; confirmed by EMSA and ChIP assays. STAT1 siRNA knockdown, STAT1 overexpression, EMSA, ChIP assay at S1PR1 promoter, luciferase reporter assay with truncated promoter fragments, IFN-γ stimulation Gene High 32006593
2021 SMYD3 promotes S1PR1 expression in hepatocellular carcinoma by methylating histone H3 at lysine 4 (H3K4me3) at the S1PR1 promoter; SMYD3 expression is positively correlated with S1PR1 in HCC and promotes HCC cell growth and migration in a manner partially dependent on S1PR1 upregulation. Chromatin immunoprecipitation (H3K4me3 at S1PR1 promoter), SMYD3 overexpression/knockdown, S1PR1 promoter activity assay, in vitro and in vivo tumor growth assays Cell death & disease Medium 34301921
2023 S1PR1 directly activates STAT3 in esophageal squamous cell carcinoma cells: co-immunoprecipitation demonstrates direct binding of S1PR1 and STAT3; S1PR1 silencing reduces STAT3 phosphorylation (p-STAT3), while S1PR1 overexpression increases p-STAT3 and promotes proliferation and suppresses apoptosis. Co-immunoprecipitation (S1PR1-STAT3 interaction), siRNA knockdown, S1PR1 overexpression, STAT3 phosphorylation western blot, in vitro and in vivo tumor assays Journal of experimental & clinical cancer research Medium 31438989
2023 In zebrafish, loss of s1pr1 disrupts astrocyte process elaboration and extension/retraction dynamics; pharmacological modulation of S1pr1 balances astrocyte process growth; functional analog of Drosophila Tre1, with loss of either causing motor behavioral defects. s1pr1 loss-of-function in zebrafish, live imaging of astrocyte process dynamics, pharmacological S1PR1 modulation, behavioral assays Neuron Medium 38096817
2019 Endothelial S1PR1 activates the AKT/eNOS signaling pathway, producing nitric oxide that inhibits cardiomyocyte hypertrophy and cardiac fibroblast transformation; endothelial-specific S1pr1 deletion aggravates pressure overload-induced cardiac hypertrophy and fibrosis; inhibition of AKT/eNOS reverses S1pr1-overexpression-mediated protection. Endothelial-specific S1pr1 KO (TAC model), S1pr1 overexpression, AKT/eNOS phosphorylation assay, NO production measurement, AKT inhibitor epistasis Journal of cellular and molecular medicine High 31854513

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. The Journal of clinical investigation 978 11032855
1998 Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science (New York, N.Y.) 854 9488656
1998 Dual actions of sphingosine-1-phosphate: extracellular through the Gi-coupled receptor Edg-1 and intracellular to regulate proliferation and survival. The Journal of cell biology 427 9660876
2001 Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science (New York, N.Y.) 370 11230698
2010 STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors. Nature medicine 342 21102457
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
2012 The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Developmental cell 271 22975327
2001 Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Molecular cell 265 11583630
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 257 11150298
2017 S1PR1 on tumor-associated macrophages promotes lymphangiogenesis and metastasis via NLRP3/IL-1β. The Journal of experimental medicine 236 28739604
1998 Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1. The Biochemical journal 233 9480864
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 226 10383399
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
1999 Ligand-induced trafficking of the sphingosine-1-phosphate receptor EDG-1. Molecular biology of the cell 169 10198065
1996 The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway. The Journal of biological chemistry 153 8626678
2001 Role of the sphingosine 1-phosphate receptor EDG-1 in vascular smooth muscle cell proliferation and migration. Circulation research 148 11557736
2001 EDG-1 links the PDGF receptor to Src and focal adhesion kinase activation leading to lamellipodia formation and cell migration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 140 11726541
2000 Agonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae. eNOS activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction. The Journal of biological chemistry 133 10921915
2012 A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis. The Journal of experimental medicine 128 23148237
2017 S1PR1 (Sphingosine-1-Phosphate Receptor 1) Signaling Regulates Blood Flow and Pressure. Hypertension (Dallas, Tex. : 1979) 114 28607130
1998 Lysophosphatidic acid stimulates the G-protein-coupled receptor EDG-1 as a low affinity agonist. The Journal of biological chemistry 107 9705355
2016 The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures. Journal of neuroinflammation 105 26856814
2019 CD4 T cell sphingosine 1-phosphate receptor (S1PR)1 and S1PR4 and endothelial S1PR2 regulate afferent lymphatic migration. Science immunology 81 30877143
2023 Sphingosine-1-phosphate derived from PRP-Exos promotes angiogenesis in diabetic wound healing via the S1PR1/AKT/FN1 signalling pathway. Burns & trauma 77 37251708
2021 Structures of signaling complexes of lipid receptors S1PR1 and S1PR5 reveal mechanisms of activation and drug recognition. Cell research 71 34526663
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
2014 MicroRNA-363-mediated downregulation of S1PR1 suppresses the proliferation of hepatocellular carcinoma cells. Cellular signalling 67 24631531
2002 N-glycans of sphingosine 1-phosphate receptor Edg-1 regulate ligand-induced receptor internalization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 66 12087059
2016 T cell-intrinsic S1PR1 regulates endogenous effector T-cell egress dynamics from lymph nodes during infection. Proceedings of the National Academy of Sciences of the United States of America 65 26862175
1997 The mouse gene for the inducible G-protein-coupled receptor edg-1. Genomics 65 9226368
2018 Targeting S1PR1/STAT3 loop abrogates desmoplasia and chemosensitizes pancreatic cancer to gemcitabine. Theranostics 63 30083262
2013 β1-adrenergic receptor and sphingosine-1-phosphate receptor 1 (S1PR1) reciprocal downregulation influences cardiac hypertrophic response and progression to heart failure: protective role of S1PR1 cardiac gene therapy. Circulation 62 23969695
2017 Targeting the S1P/S1PR1 axis mitigates cancer-induced bone pain and neuroinflammation. Pain 61 28570482
2014 Hypothalamic S1P/S1PR1 axis controls energy homeostasis. Nature communications 61 25255053
2019 S1PR1 as a Novel Promising Therapeutic Target in Cancer Therapy. Molecular diagnosis & therapy 60 31115798
2020 S1PR1 regulates the quiescence of lymphatic vessels by inhibiting laminar shear stress-dependent VEGF-C signaling. JCI insight 59 32544090
2004 Regulation of limb development by the sphingosine 1-phosphate receptor S1p1/EDG-1 occurs via the hypoxia/VEGF axis. Developmental biology 57 15063179
2000 Sphingosine 1-phosphate: a ligand for the EDG-1 family of G-protein-coupled receptors. Annals of the New York Academy of Sciences 57 10818441
2018 Endoplasmic reticulum resident oxidase ERO1-Lalpha promotes hepatocellular carcinoma metastasis and angiogenesis through the S1PR1/STAT3/VEGF-A pathway. Cell death & disease 55 30377291
2016 S1PR1-mediated IFNAR1 degradation modulates plasmacytoid dendritic cell interferon-α autoamplification. Proceedings of the National Academy of Sciences of the United States of America 55 26787880
2018 SPHK1-S1PR1-RANKL Axis Regulates the Interactions Between Macrophages and BMSCs in Inflammatory Bone Loss. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 53 29377379
2021 Vascular endothelial S1pr1 ameliorates adverse cardiac remodelling via stimulating reparative macrophage proliferation after myocardial infarction. Cardiovascular research 51 32091582
2004 Atypical cannabinoid stimulates endothelial cell migration via a Gi/Go-coupled receptor distinct from CB1, CB2 or EDG-1. European journal of pharmacology 51 15063151
2016 PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis. Molecular imaging and biology 49 26975859
2000 Expression and characterization of Edg-1 receptors in rat cardiomyocytes: calcium deregulation in response to sphingosine 1-phosphate. European journal of biochemistry 47 10971577
2019 S1PR1 promotes proliferation and inhibits apoptosis of esophageal squamous cell carcinoma through activating STAT3 pathway. Journal of experimental & clinical cancer research : CR 45 31438989
2010 The sphingosine 1-phosphate receptor, S1PR₁, plays a prominent but not exclusive role in enhancing the excitability of sensory neurons. Journal of neurophysiology 45 20844107
2016 A MicroRNA302-367-Erk1/2-Klf2-S1pr1 Pathway Prevents Tumor Growth via Restricting Angiogenesis and Improving Vascular Stability. Circulation research 42 27756792
2000 Sphingosine-1-phosphate signaling via the EDG-1 family of G-protein-coupled receptors. Annals of the New York Academy of Sciences 42 10818438
2000 Differential roles of Edg-1 and Edg-5, sphingosine 1-phosphate receptors, in the signaling pathways in C6 glioma cells. Brain research. Molecular brain research 42 11146117
2014 Dynamin 2-dependent endocytosis is required for sustained S1PR1 signaling. The Journal of experimental medicine 41 24638168
2001 The sphingosine-1-phosphate receptor EDG-1 is essential for platelet-derived growth factor-induced cell motility. Biochemical Society transactions 41 11709084
2019 Endothelial S1pr1 regulates pressure overload-induced cardiac remodelling through AKT-eNOS pathway. Journal of cellular and molecular medicine 40 31854513
2016 S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization. Journal of lipid research 40 27881715
2022 S1PR1 induces metabolic reprogramming of ceramide in vascular endothelial cells, affecting hepatocellular carcinoma angiogenesis and progression. Cell death & disease 38 36068200
2019 S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer. Cell death & disease 36 30814488
2012 Critical role of S1PR1 and integrin β4 in HGF/c-Met-mediated increases in vascular integrity. The Journal of biological chemistry 36 23212923
2019 S1P-S1PR1 Signaling: the "Sphinx" in Osteoimmunology. Frontiers in immunology 35 31293578
2018 Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus. PloS one 35 29608575
2018 S1P promotes inflammation-induced tube formation by HLECs via the S1PR1/NF-κB pathway. International immunopharmacology 34 30476824
2022 S1P/S1PR1 signaling differentially regulates the allogeneic response of CD4 and CD8 T cells by modulating mitochondrial fission. Cellular & molecular immunology 33 36071219
2021 InVitro and In Vivo Investigation of S1PR1 Expression in the Central Nervous System Using [3H]CS1P1 and [11C]CS1P1. ACS chemical neuroscience 33 34516079
2020 Post-translational modifications of S1PR1 and endothelial barrier regulation. Biochimica et biophysica acta. Molecular and cell biology of lipids 31 32585303
2019 Combination of sphingosine-1-phosphate receptor 1 (S1PR1) agonist and antiviral drug: a potential therapy against pathogenic influenza virus. Scientific reports 31 30918324
1994 Cloning of the rat edg-1 immediate-early gene: expression pattern suggests diverse functions. Gene 31 7959012
2023 Transmembrane protein CD69 acts as an S1PR1 agonist. eLife 30 37039481
2021 aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete, β-arrestin-2-mediated SphK1-S1PR1-Akt signaling axis. Proceedings of the National Academy of Sciences of the United States of America 29 34873055
2021 Blocking SphK1/S1P/S1PR1 Signaling Pathway Alleviates Lung Injury Caused by Sepsis in Acute Ethanol Intoxication Mice. Inflammation 28 34109517
2020 Genomewide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy. Clinical pharmacology and therapeutics 28 32562552
2023 Dexmedetomidine alleviates oxidative stress and mitochondrial dysfunction in diabetic peripheral neuropathy via the microRNA-34a/SIRT2/S1PR1 axis. International immunopharmacology 26 37012886
2017 Sphingosine 1-phosphate receptor 1 (S1PR1) agonist CYM5442 inhibits expression of intracellular adhesion molecule 1 (ICAM1) in endothelial cells infected with influenza A viruses. PloS one 26 28399143
2015 S1PR1 Tyr143 phosphorylation downregulates endothelial cell surface S1PR1 expression and responsiveness. Journal of cell science 26 25588843
2014 Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation. PloS one 26 25188412
2012 CCR7/CCL19 controls expression of EDG-1 in T cells. The Journal of biological chemistry 26 22334704
2020 In vivo Characterization of Four 18F-Labeled S1PR1 Tracers for Neuroinflammation. Molecular imaging and biology 25 32602083
2024 Kaempferol mitigates sepsis-induced acute lung injury by modulating the SphK1/S1P/S1PR1/MLC2 signaling pathway to restore the integrity of the pulmonary endothelial cell barrier. Chemico-biological interactions 24 38823539
2017 S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells. Leukemia 24 28878352
2015 S1PR1 expression correlates with inflammatory responses to Newcastle disease virus infection. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 24 26597451
2014 Host endothelial S1PR1 regulation of vascular permeability modulates tumor growth. American journal of physiology. Cell physiology 24 24740542
2023 S1P/S1PR1 axis promotes macrophage M1 polarization through NLRP3 inflammasome activation in Lupus nephritis. Molecular immunology 23 37379683
2021 SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters. Cell death & disease 23 34301921
2023 Astrocyte growth is driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor. Neuron 22 38096817
2020 Coinhibition of S1PR1 and GP130 by siRNA-loaded alginate-conjugated trimethyl chitosan nanoparticles robustly blocks development of cancer cells. Journal of cellular physiology 22 32424937
2015 Sphingosine-1-phosphate receptor 1 (S1PR1) expression in non-muscle invasive urothelial carcinoma: Association with poor clinical outcome and potential therapeutic target. European journal of cancer (Oxford, England : 1990) 22 26238015
2024 S1PR1 inhibition induces proapoptotic signaling in T cells and limits humoral responses within lymph nodes. The Journal of clinical investigation 21 38194271
2023 Siponimod exerts neuroprotective effects on the retina and higher visual pathway through neuronal S1PR1 in experimental glaucoma. Neural regeneration research 21 36204852
2023 Force-Loaded Cementocytes Regulate Osteoclastogenesis via S1P/S1PR1/Rac1 Axis. Journal of dental research 21 37735908
2023 S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma. Journal of experimental & clinical cancer research : CR 20 36600310
2023 S1PR1 regulates ovarian cancer cell senescence through the PDK1-LATS1/2-YAP pathway. Oncogene 20 37828220
2022 SphK1 Promotes Cancer Progression through Activating JAK/STAT Pathway and Up-Regulating S1PR1 Expression in Colon Cancer Cells. Anti-cancer agents in medicinal chemistry 20 33797381
2019 Macrophage S1PR1 Signaling Alters Angiogenesis and Lymphangiogenesis During Skin Inflammation. Cells 20 31357710
2018 Sphingosine 1 phosphate receptor-1 (S1PR1) signaling protects cardiac function by inhibiting cardiomyocyte autophagy. Journal of geriatric cardiology : JGC 20 30083186
2023 Aralia saponin A isolated from Achyranthes bidentata Bl. ameliorates LPS/D-GalN induced acute liver injury via SPHK1/S1P/S1PR1 pathway in vivo and in vitro. International immunopharmacology 19 37699301
2019 Potential involvement of S1PR1/STAT3 signaling pathway in cardiac valve damage due to rheumatic heart disease. Biotechnic & histochemistry : official publication of the Biological Stain Commission 19 30712389
2016 miR-133b, a microRNA targeting S1PR1, suppresses nasopharyngeal carcinoma cell proliferation. Experimental and therapeutic medicine 18 27073467
2021 S1PR1 signaling in cancer: A current perspective. Advances in protein chemistry and structural biology 17 33931142
2021 miR-145-5p exerts anti-tumor effects in diffuse large B-cell lymphoma by regulating S1PR1/STAT3/AKT pathway. Leukemia & lymphoma 16 33715582
2020 STAT1 transcriptionally regulates the expression of S1PR1 by binding its promoter region. Gene 16 32006593
2020 S1PR1-Associated Molecular Signature Predicts Survival in Patients with Sepsis. Shock (Augusta, Ga.) 16 32045395

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