• The EDG receptors couple to multiple G proteins to signal through Ras, MAP kinase, Rho, Phospholipase C or other tyrosine kinases, which lead to cell survival, growth, migration and differentiation. (acris-antibodies.com)
  • To identify novel effectors downstream of the TCR, we designed a retroviral-based functional genetic screen to select for proteins that inhibit receptor-mediated T cell activation. (jimmunol.org)
  • Treatment of juvenile TG mice with pitavastatin, an established inhibitor of the Rho family G proteins, or deletion of S1P3, a major myocardial S1P receptor subtype that couples to Rho GTPases and transactivates Smad signalling, both inhibited cardiac fibrosis with concomitant inhibition of SPHK1-dependent Smad-3 phosphorylation. (elsevier.com)
  • Real-time PCR and Western blot analysis demonstrated the expression of the S1P receptor transcript pools and corresponding proteins including S1P1, S1P2, and S1P3 in tissues dissected from sinoatrial node, atrium and ventricle. (ox.ac.uk)
  • This protein functions as a lysophosphatidic acid (LPA) receptor and contributes to Ca2+ mobilization, a critical cellular response to LPA in cells, through association with Gi and Gq proteins. (mybiosource.com)
  • In stably transfected CHO (Chinese-hamster ovary) cell lines expressing the S1P receptors S1PR1 or S1PR3, NOX-S93 inhibits S1P-mediated β-arrestin recruitment and intracellular calcium release respectively, with IC50 values in the low nanomolar range. (nih.gov)
  • Methods: Concurrent to VEGFR blockade in mice, S1P signaling augmentation was achieved via treatment with the S1P precursor sphingosine, S1P agonist FTY720, or S1P receptor-1 (S1PR1) agonist SEW2871. (elsevier.com)
  • Sphingosine-1-phosphate (S1P) and S1P-receptor-1 (S1PR1) promote lymphocyte egress from white to red pulp and back to circulation. (ox.ac.uk)
  • S1P interaction with its receptor S1PR1 is needed for the egress of immune cells from the lymphoid organs (such as thymus and lymph nodes) into the lymphatic vessels. (wikipedia.org)
  • S1P1 was the first identified S1P receptor. (creativebiomart.net)
  • Treatment with S1P1 receptor inhibitor (W146) for 4 days after induction of adipogenesis attenuated adipocyte differentiation. (yonsei.ac.kr)
  • S1P1 receptor inhibitor reduced the number of adipocytes and suppressed the accumulation of lipid droplets induced by 10 μM H2O2 or 2% cigarette smoke extract (CSE) treatment. (yonsei.ac.kr)
  • B lymphocyte egress from secondary lymphoid organs requires sphingosine-1-phosphate (S1P) and S1P receptor-1 (S1P1).Transgenic expression of S1P1 in developing B cells was sufficient to mobilize pro- and pre-B cells from the BM.We conclude that the S1P1-S1P pathway contributes to egress of immature-B cells from BM, and that this mechanism is partially redundant with other undefined pathways. (nih.gov)
  • B lymphocyte egress from secondary lymphoid organs requires sphingosine-1-phosphate (S1P) and S1P receptor-1 (S1P1). (nih.gov)
  • Flow cytometric analysis of BM parenchymal and sinusoidal naïve CD4+ T cells showed detectable surface S1P1 on parenchymal cells compared to a lack of surface receptor on sinusoidal cells (Figure 3A) as recently reported , indicating that S1P concentrations are lower in the parenchyma than in sinusoids. (nih.gov)
  • Although all three S1P receptor isoforms were expressed in AVN tissues, S1P1 receptor isoform expression level was higher than S1P2 and S1P3. (ox.ac.uk)
  • Sphingosine 1-phosphate (S1P, 1) regulates vascular barrier and lymphoid development, as well as lymphocyte egress from lymphoid organs, by activating high-affinity S1P1 receptors. (scripps.edu)
  • Vascular (but not airway) administration of the preferred R enantiomer of an in vivo-active chiral S1P1 receptor antagonist induced loss of capillary integrity in mouse skin and lung. (scripps.edu)
  • The sphingosine 1-phosphate receptor subtype 1 (S1P1R) is modulated by phosphorylated FTY720 (pFTY720), which causes S1P1R internalization preventing lymphocyte migration thus limiting autoimmune response. (nih.gov)
  • Sphingosine kinases (Sphk1, Sphk2) phosphorylate FTY720 in vivo to form the bioactive metabolite FTY720-1- phosphate (FTY720-P). Cytoplasmic FTY720-P is an agonist for 4 of the 5 sphingosine-1-phosphate (S1P) receptors (S1P 1,3-5 ) and can also act as a functional antagonist of S1P 1 , whereas FTY720-P generated in the nucleus inhibits histone deacetylases (HDACs), leading to increased histone acetylation. (elsevier.com)
  • The results of this study suggest that FTY720-induced NTDs may involve multiple mechanisms, including: (1) sustained and/or altered S1P receptor activation and signaling by FTY720-P produced in the cytoplasm and (2) HDAC inhibition and histone hyperacetylation by FTY720-P generated in the nucleus that could lead to epigenetic changes in gene regulation. (elsevier.com)
  • To evaluate the effect of S1P and S1P receptor blockers (W146 and FTY720) on adipocyte differentiation, cultures were exposed to each receptor blocker for the first 4 days of the differentiation period. (yonsei.ac.kr)
  • METHODS: Pregnant SWV and LM/Bc mice were treated with FB 1 (20 mg/kg/day intraperitoneally on embryonic day (ED) 7.5-8.5) or the known S1P receptor agonist FTY720 (10 mg/kg/day oral gavage on ED 6.5-8.5). (elsevier.com)
  • We excluded S1P as one of the host related factor which influences AMD3100 directed mobilization because pre-treatment of S1P receptor antagonist FTY720 did not inhibit BMSPC mobilization. (bvsalud.org)
  • The sphingosine-1-phosphate (S1P) receptor modulator, fingolimod (FTY720), has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular (AV) conduction block have been reported in some patients after the first dose. (ox.ac.uk)
  • When administered to mice, an antagonist blocked the lymphopenia evoked by a S1P receptor agonist and caused capillary leakage in both lung and kidney. (nih.gov)
  • The lymphopenia evoked by the S1P agonist, 12b ( VPC44152 ) is blocked by co-administration of the S1P receptor antagonist 12d ( VPC44116 ). (nih.gov)
  • Therapeutics that impact remyelination in the CNS could be critical determinants of long-term functional outcome in multiple sclerosis (MS). Fingolimod is a S1P receptor modulator in MS clinical trials due to systemic anti-inflammatory properties, yet may impact cells within the CNS by crossing the blood-brain barrier. (nih.gov)
  • Previous studies using isolated dissociated cultures indicate that neural cells express S1P receptors and respond to receptor engagement. (nih.gov)
  • Title: Inhibition of autophagy and chemokine induction by sphingosine 1-phosphate receptor 1 through NF-κB signaling in human pulmonary endothelial cells infected with influenza A viruses. (nih.gov)
  • In vivo studies showed that pancreatic cancer cells co-implanted with S1P2 receptor knockdown PSCs led to less cancer growth and metastasis in s.c. and orthotopic pancreatic cancer models compared with control PSCs. (elsevier.com)
  • The PAK2 truncation, PAK2ΔL, blocked Ag receptor-induced NFAT activation and TCR-mediated calcium flux in Jurkat T cells. (jimmunol.org)
  • Treatment of HA-S1P2 over-expressing MDA-MB-231 cells with the sphingosine 1-phosphate receptor-4 (S1P4) antagonist CYM50367 or with S1P4 siRNA also promoted nuclear translocation of HA-tagged S1P2. (strath.ac.uk)
  • These findings identify for the first time a signaling pathway in which sphingosine 1-phosphate formed by sphingosine kinase 2 binds to S1P4 to prevent nuclear translocation of S1P2 and thereby promote the growth of estrogen receptor negative breast cancer cells. (strath.ac.uk)
  • Rationale: Vascular endothelial growth factor receptor (VEGFR) inhibition increases ceramides in lung structural cells of the alveolus, initiating apoptosis and alveolar destruction morphologically resembling emphysema. (elsevier.com)
  • S1P receptor levels in human brain choroid plexus endothelial cells (CPEC), human lung microvascular endothelial cells, human retinal vascular endothelial cells, and circulating endothelial progenitor cells were examined by semi-quantitative PCR. (elsevier.com)
  • S1P promoted in vitro capillary tube formation in CPEC consistent with the presence of cognate S1P 1-5 receptor expression by these cells and the S1P antibody induced a dose-dependent reduction in microvessel tube formation. (elsevier.com)
  • Sphingosine-1-phosphate stimulates the functional capacity of progenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptor. (unboundmedicine.com)
  • Sphingosine-1-phosphate (S1P) is a bioactive lipid, which influences migration and proliferation of endothelial cells through activation of S1P receptors and has been shown to support SDF-1 induced migration and bone marrow homing of CD34+ progenitors. (unboundmedicine.com)
  • Non-peptide antigen presentation to T-cell receptors on NKT cells, marks T-cells at the short cortical thymic stage of differentiation. (abcam.co.jp)
  • Non peptide antigen presentation to T-cell receptors on NKT cells. (abcam.co.jp)
  • Inhibition of lymphocyte recirculation by activation of S1P receptors may result in therapeutically useful immunosuppression. (sciencemag.org)
  • Finally, in vivo effects of LP receptor gene deletion in mice will be discussed. (nih.gov)
  • Likewise, recovery of blood flow was dramatically reduced after induction of hindlimb ischemia in mice deficient for the S1P receptor 3 (S1P3). (unboundmedicine.com)
  • The activation of the CXCR4 signaling by S1P is mediated via the S1P3 receptor, since S1P-induced Src phosphorylation was abrogated in EPC from S1P3-/- mice. (unboundmedicine.com)
  • The analogous R150H substitution of the DRY motif in zebrafish sphingosine-1 phosphate receptor 2 (S1p2) produces a mutation, miles apart m(93) (mil(m93)), that not only disrupts signaling but also impairs heart field migration. (duke.edu)
  • Objectives: The aims of our work were to investigate the sphingosine-S1P-S1P receptor axis in the VEGFR inhibition model of emphysema and to determine whether stimulation of S1P signaling is sufficient to functionally antagonize alveolar space enlargement. (elsevier.com)
  • S1P receptor agonists induced emptying of lymphoid sinuses by retention of lymphocytes on the abluminal side of sinus-lining endothelium and inhibition of egress into lymph. (sciencemag.org)
  • Inhibition of S1P receptors was shown to be critical for immunomodulation. (wikipedia.org)
  • We present the novel finding that low, subcontractile concentrations of SPC potentiate Ca 2+ entry in intrapulmonary arteries through both voltage-dependent and independent pathways via a receptor-dependent mechanism involving PKCδ. (ahajournals.org)