ライフサイエンスコーパス: S1P

1 S1P (Sphingosine 1-phosphate) signaling coordinates vasc

2 S1P activation of nodose C-fibres does not occur in S1PR

3 S1P activation of nodose C-fibres is inhibited by a S1PR

4 S1P can bind to several G-protein-coupled receptors (GPC

5 S1P can function so effectively because its distribution

6 S1P lyase (SGPL1) knockout in either immune cells or tis

7 S1P promotes cell growth, survival, and migration and is

8 S1P regulates diverse cell activities via S1P receptors

9 S1P serum level in humans was correlated with endothelia

10 S1P signaling has been reported to regulate different as

11 S1P signalling maintains the mitochondrial content of na

12 S1P specifically binds to the PAS domains of HIF-1alpha.

13 S1P(1) signaling sustains hallmark endothelial functions

14 Therefore, as d16:1 S1P concentration increases, it is likely to disproporti

15 Although d16:1 S1P is an S1P(2) agonist, it has lower potency than the

16 pecifically increases one S1P species, d16:1 S1P, in these patients.

17 cy than the most abundant S1P species (d18:1 S1P).

18 Sphingosine-1 phosphate receptor-1 (S1P(1)) plays fundamental physiological roles in endothe

19 cular functions in other organs, and S1P(1) (S1P receptor-1) modulators including fingolimod show pro

20 umors with upregulated sphingosine kinase 1, S1P receptor 2 and epidermal growth factor receptor.

21 ndent upon proteolytic cleavage by the SKI-1/S1P protease.

22 cryptococcosis from the granuloma through a S1P receptor 3-mediated mechanism and support the ration

23 it has lower potency than the most abundant S1P species (d18:1 S1P).

24 site effect, namely, the ability to activate S1P(1,) could help to restore endothelial homeostasis.

25 SAR247799 activated S1P(1) on endothelium without causing receptor desensiti

26 bolite that is required for activity against S1P(1).

27 Although d16:1 S1P is an S1P(2) agonist, it has lower potency than the most abund

28 actively exit via efferent lymphatics via an S1P dependent mechanism.

29 which was partially rescued by VPC23109, an S1P receptor antagonist.

30 With an S1P(1) signaling reporter, we reveal that abluminal pola

31 have higher expression of LPA receptor 1 and S1P receptor 3 compared with normal kidney.

32 Knockdown studies suggest that S1P(2) and S1P(3) mediate this effect by activating myocardin-relat

33 e activation of cognate receptors S1P(2) and S1P(3).

34 lial cells, linking loss of SK2 activity and S1P in AD to perturbed endosomal lipid metabolism.

35 inocytes (KC); 2) increases in both CAMP and S1P production depend upon differentiation level of KC (

36 Adipocytes, as well as CXCR4-CXCL12 and S1P-S1P(1)R interactions, contributed to enhanced T cell

37 eover, increases in the SphK1 expression and S1P levels were observed in human lupus patients.

38 ued upon cotreatment with PLD inhibitors and S1P.

39 evealed transcriptomic signatures of LPA and S1P, suggesting an LPA/S1P-mediated reprogramming of the

40 We describe MC and S1P as novel pathogenic effectors that initiate remodeli

41 ates vascular functions in other organs, and S1P(1) (S1P receptor-1) modulators including fingolimod

42 ndothelial heterogeneity, GPCR signaling and S1P biology.

43 of 2 to breast cancer cells enhanced SK1 and S1P levels, triggering a migratory phenotype.

44 induces SNAI2 expression via S1P(2)-YAP and S1P(3)-MRTF-A pathways, leading to enhanced cell invasio

45 Ozanimod, another S1P receptor modulator in the approval stage that also t

46 association between apo M and HDL-associated S1P.

47 ng ischemia by engagement of cell-autonomous S1P provision.

48 cadherin, platelet-derived growth factor B, S1P(1), and CCN1 (molecules associated with angiogenesis

49 ted that inhibition of SphK2 increases blood S1P levels.

50 In both S1P- and S. aureus bacterial supernatant-treated normal

51 Thus, apoM-bound S1P maintains low paracellular BBB permeability in all c

52 Phosphate moiety of the surface bound S1P engages in a highly positive region close to alpha1-

53 sed delayed tumor formation characterized by S1P receptor 1, STAT3 mRNA increase, as well as programm

54 naive T cells were readily chemoattracted by S1P in an FTY720-sensitive, S1PR1-dependent manner.

55 the ischemic penumbra that is coordinated by S1P signaling and can be harnessed for neuroprotection w

56 There, they are cleaved first by S1P and then by S2P, liberating their N-terminal domains

57 Action potential generation by S1P in nodose C-fibres was effectively inhibited by the

58 ggesting that liver defects were mediated by S1P accumulation.

59 n of cancer-associated proteins regulated by S1P.

60 er, we show that early activation of RhoA by S1P inactivates Rac1 but not Cdc42, and vice versa.

61 In the ischemic brain, endothelial cell S1P(1) supports blood-brain barrier function, microvascu

62 In HeLa cells, S1P-dependent activation of aPKC suppressed apoptosis.

63 ws that depending on the initiating cellular S1P source, the pathophysiology of inflammation-induced

64 MI HF progression in mice as much as chronic S1P treatment.

65 R knockout mice does not elevate circulating S1P levels, nor does it ameliorate post-MI dysfunction,

66 eta1AR-blockers display elevated circulating S1P levels, confirming that Meto promotes S1P secretion/

67 e organ adaptation that involves circulating S1P chaperone ApoM(+) high density lipoprotein (HDL), wh

68 Circulatory S1P has critical roles in maturation and homeostasis of

69 In contrast, circulatory S1P-dependent S1PR1/B-arrestin coupling was observed in

70 Thus, circulatory S1P confinement could be a primordial strategy of verteb

71 atory fluids, and binds to G protein-coupled S1P receptors (S1PRs) to regulate embryonic development,

72 These compounds effectively decrease S1P levels in vitro.

73 ypes, including a delay in epiboly, depleted S1P levels, elevated levels of sphingosine, and resistan

74 ed minimal renal protection and desensitized S1P(1) These findings demonstrate that sustained S1P(1)

75 cation of BMS-986104 (2) as a differentiated S1P(1) receptor modulator.

76 cal vascular protective role for endothelial S1P(1) in the mouse brain.

77 lly manipulating the S1P-metabolizing enzyme S1P lyase (SPL).

78 Here, we report that increased erythrocyte S1P binds to deoxygenated sickle Hb (deoxyHbS), facilita

79 ceptor are desensitizing and are essentially S1P(1) functional antagonists that cause lymphopenia.

80 ological crypt remodeling plus extracellular S1P-signaling caused delayed tumor formation characteriz

81 ues 527, 528, and 530, which are crucial for S1P cleavage.

82 ion and reveal a previously unknown role for S1P in positioning cells within the medulla.

83 These results indicate a role for S1P signaling in B. pertussis-mediated pathology and hig

84 m of aPKC regulation, a molecular target for S1P in cell survival regulation, and a tool to further e

85 ewed as the principal therapeutic target for S1P(1) modulation in stroke.

86 1) signaling, shifting the balance away from S1P(2) We further show that a selective S1P(2) agonist,

87 ates thymic exit via a process distinct from S1P-mediated migration.

88 ociated with reduced survival signaling from S1P receptor 2, resulting in selective downregulation of

89 effects by binding to the following 5 GPCRs: S1P(1) to S1P(5).

90 liver tissue from mice and patients, hepatic S1P levels increased owing to increased hepatic sphingos

91 d an inverse correlation between hippocampal S1P levels and age in females, leading us to speculate t

92 important to build an integrated view of how S1P shapes inflammation.

93 Here we review how S1P gradients regulate immune cell exit from tissues, wi

94 However, S1P(1) also coordinates lymphocyte trafficking, and lymp

95 To determine if S1P formation in the nucleus by SphK2 is a key regulator

96 ate the capability of this system by imaging S1P(1)-eGFP-Human bone osteosarcoma epithelial (U2OS) ce

97 ion of SREBP1 variants demonstrated impaired S1P cleavage, which prohibited nuclear translocation of

98 We hypothesize that changes in S1P signaling are central to the inflammatory and immune

99 by endothelial cell-selective deficiency in S1P production, export, or the S1P(1) receptor substanti

100 MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells.

101 f inflammation and associated with increased S1P generation.

102 Indeed, S1P can be considered a circulation marker, signaling to

103 re and function at doses that did not induce S1P(1)-desensitizing effects, such as lymphopenia and lu

104 Mechanistically, we found that Meto-induced S1P secretion is beta3AR-dependent because Meto infusion

105 ureus bacterial supernatant not only induced S1P production but also increased the transcription of S

106 attractive chemotypes capable of inhibiting S1P formation in cells.

107 Intracellular S1P directly bound to the purified kinase domain of aPKC

108 ficantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfec

109 how aberrant extracellular and intracellular S1P signaling contributes to the pathogenesis and progre

110 e, we investigated the role of intracellular S1P in insulin-secreting INS1E cells by genetically mani

111 ve in restoring resistance after a 1 mumol/L S1P challenge as compared with the DU145 alpha6WT cells.

112 he use of a reporter for the signaling lipid S1P (sphingosine 1-phosphate), we found that cells sense

113 yme SK2, which generates the signaling lipid S1P, is required for Abeta formation from APP in vivo Se

114 signatures of LPA and S1P, suggesting an LPA/S1P-mediated reprogramming of the TSC lipidome.

115 s study identifies activation of the ATX-LPA/S1P pathway as a novel mode of metabolic dysregulation u

116 , which contributed to a reduced liver:lymph S1P gradient and limited HSC egress from the liver.

117 nd lymphopenia induced by loss of lymphocyte S1P(1) provides modest protection only in the context of

118 search is needed to assess whether the apo M/S1P axis is a suitable therapeutic target in heart failu

119 Finally, in S1PR3 knockout mice, S1P was not able to activate any of the airway nodose C-

120 Moreover, S1P/S1PR1 signaling regulates the expression of lymphang

121 g influences such as loss of neuroprotective S1P are more important drivers of neurodegeneration than

122 Nuclear S1P is involved in epigenetic regulation of gene express

123 work, we have identified the role of nuclear S1P and SphK2 in regulating hypoxia-responsive master tr

124 elective SphK2 inhibitor K-145, that nuclear S1P, histone acetylation, HIF-1alpha expression, and TNB

125 rify the complex and wide ranging actions of S1P but also guide the development of therapeutics and t

126 parison to fingolimod (1), a full agonist of S1P(1) currently marketed for the treatment of relapse r

127 found and characterized a biased agonist of S1P(1), SAR247799, which preferentially activated downst

128 discover highly potent, partial agonists of S1P(1) with a shorter T(1/2) and increased in vivo phosp

129 ces chemotaxis towards low concentrations of S1P and stimulates motility.

130 d that cells sensed higher concentrations of S1P in the medullary cords than in the T cell zone and t

131 ration of GSCs towards low concentrations of S1P in vitro In addition, inhibiting phospholipase A2 (P

132 cks chemotaxis towards low concentrations of S1P.

133 GSCs migrating towards low concentrations of S1P.

134 ases in ceramide and consequent decreases of S1P reduce proliferation of various cancers, AC might of

135 In patients, several side effects of S1P(1) desensitization have been attributed to endotheli

136 The formation of S1P is catalyzed by sphingosine kinase 1 or 2 (SphK1 or

137 Physiological functions of S1P are tightly linked to shear stress, the key biophysi

138 hat SPL's pro-IFN function is independent of S1P.

139 on of SphK1 and SphK2 to attenuate levels of S1P has been reported to be efficacious in animal models

140 Levels of S1P in liver, bone marrow, and lymph fluid were measured

141 We have reported pronounced loss of S1P and SK2 activity early in Alzheimer's disease (AD) p

142 emales, leading us to speculate that loss of S1P is a sensitizing influence for AD.

143 (APP) in vitro To determine whether loss of S1P sensitizes to Abeta-mediated neurodegeneration, we i

144 Using spatial modulation of S1P provision and signaling, we demonstrate a critical v

145 We demonstrate a novel outcome of S1P-mediated regulation of lymphocyte trafficking, where

146 lso challenge previous models of the role of S1P in lymphocyte recirculation and suggest that S1P pro

147 Here, we summarize the role of S1P in pain to highlight the potential of targeting the

148 This review will focus on the role of S1P in renal cells and how aberrant extracellular and in

149 o studies and highlight the potential use of S1P receptors as drug targets for treatment of Krabbe's

150 ent and energizing drug discovery focused on S1P signaling.

151 nodes in a CD62L-dependent way and relied on S1P receptors for their exit.

152 iplatin treatment specifically increases one S1P species, d16:1 S1P, in these patients.

153 tion 7 cells stably overexpressing S1P(2) or S1P(3) exhibit a more invasive phenotype, when compared

154 BH3 mimetics with either SPHK1 inhibition or S1P receptor 2 antagonism triggered synergistic AML cell

155 In addition, supplementation of LPA or S1P rescued proliferation and viability, neutral lipid c

156 cer Foundation 7 cells stably overexpressing S1P(2) or S1P(3) exhibit a more invasive phenotype, when

157 pool with a blood-brain barrier penetrating S1P(1)-selective agonist can further reduce cortical inf

158 tection with blood-brain barrier-penetrating S1P(1) agonists.

159 at deficiency of the sphingosine-1-phoshate (S1P) transporter gene Spns2 in endothelium increased imm

160 The role of sphingosine-1 phosphate (S1P) in leukocyte trafficking has been well deciphered i

161 h Factor (VEGF) and Sphingosine-1 Phosphate (S1P).

162 ations of SphK1 and sphingosine 1 phosphate (S1P).

163 the bioactive lipid sphingosine 1-phosphate (S1P) and has established roles in tumor initiation, prog

164 It is an analog of sphingosine-1-phosphate (S1P) and targets S1P receptors 1, 3, 4, and 5.

165 ctivation and local sphingosine-1-phosphate (S1P) are significantly augmented after OVA treatment in

166 ovide evidence that sphingosine-1-phosphate (S1P) generated in the dorsal horn of the spinal cord in

167 ess is directed by a Sphigosine-1-Phosphate (S1P) gradient.

168 The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid

169 Chronic sphingosine-1-phosphate (S1P) infusion resulted in a development of significantly

170 Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator generated when a cell

171 Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator, generated by sphingo

172 Sphingosine 1-phosphate (S1P) is a lipid-based signaling molecule involved in neu

173 Sphingosine 1-phosphate (S1P) is a multifunctional bioactive sphingolipid involve

174 Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts

175 Sphingosine 1-phosphate (S1P) is a potent vasculoprotective and neuroprotective s

176 Sphingosine-1-phosphate (S1P) is generated through phosphorylation of sphingosine

177 tation of inducible sphingosine-1-phosphate (S1P) lyase knockout mice to specifically modulate sphing

178 GPL1, which encodes sphingosine-1-phosphate (S1P) lyase.

179 the lipid mediator sphingosine 1-phosphate (S1P) may be one such mechanism.

180 Sphingosine-1-phosphate (S1P) mediates egress of immune cells from the lymphoid o

181 The signaling lipid sphingosine 1-phosphate (S1P) plays critical roles in an immune response.

182 Sphingosine 1-phosphate (S1P) produces significant endothelial barrier enhancemen

183 phingosine used for sphingosine-1-phosphate (S1P) production.

184 the lipid mediator sphingosine 1-phosphate (S1P) promoted the cellular activity of aPKC.

185 ed the potential of sphingosine 1-phosphate (S1P) receptor (S1PR) agonism in the treatment of infecti

186 Functional sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) antagonists, such as FTY720/fing

187 he cardioprotective sphingosine-1-phosphate (S1P) receptor-1 (S1PR1).

188 role of endothelial sphingosine 1-phosphate (S1P) receptor-1, a G protein-coupled receptor known to p

189 tein M (apoM)-bound sphingosine 1-phosphate (S1P) signaling pathway affects the BBB in different cate

190 The sphingosine-1-phosphate (S1P) signaling pathway is an attractive drug target due

191 is leads to reduced sphingosine-1-phosphate (S1P) signaling via the S1P receptor 1 (S1PR1) in the vas

192 Sphingosine-1-phosphate (S1P) strongly activates mouse vagal C-fibres in the airw

193 sis was observed in sphingosine-1-phosphate (S1P) transporter spinster homologue 2 (Spns2)-deficient

194 However, levels of sphingosine-1-phosphate (S1P) were significantly increased in Ormdl3(Delta2-3/Del

195 uated the effect of sphingosine-1-phosphate (S1P), a lipid that is elevated during airway inflammator

196 Sphingosine 1-phosphate (S1P), a metabolic product of cell membrane sphingolipids

197 ve bioactive lipid, sphingosine-1-phosphate (S1P), could ameliorate the microvascular leakage followi

198 o the production of sphingosine 1-phosphate (S1P), ERK1/2 and matriptase activation via S1P receptor

199 n be metabolized to sphingosine-1-phosphate (S1P), linked to inflammation and tumorigenesis.

200 d the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in bot

201 etabolites, such as sphingosine-1-phosphate (S1P), play important roles as second messengers regulati

202 golipid metabolite, sphingosine 1-phosphate (S1P), plays a critical role in the pDC functions and int

203 ER) stress-mediated sphingosine-1-phosphate (S1P)- dependent mechanism of CAMP synthesis.

204 l proliferation and sphingosine-1-phosphate (S1P)-dependent entosis and apical cell extrusion.

205 (HDL) particles and sphingosine-1-phosphate (S1P).

206 ced levels of brain sphingosine-1-phosphate (S1P).

207 the biosynthesis of sphingosine 1-phosphate (S1P).

208 es, sphingosine and sphingosine 1-phosphate (S1P).

209 ed receptor agonist sphingosine-1-phosphate (S1P).

210 -signaling molecule sphingosine-1-phosphate (S1P).

211 idic acid (LPA) and sphingosine-1-phosphate (S1P).

212 abolite to generate sphingosine-1-phosphate (S1P).

213 signaling molecule sphingosine-1-phosphate (S1P).

214 de (-50 +/- 3%) and sphingosine 1-phosphate (S1P, -40 +/- 4%), which ended up to reduction in cell mo

215 bioactive sphingosine-1-phosphatephosphate (S1P) is present in plasma, bound to carrier proteins, an

216 he effects of platinum-based drugs on plasma S1P levels in human cancer patients.

217 disproportionately activate proinflammatory S1P(1) signaling, shifting the balance away from S1P(2)

218 ng S1P levels, confirming that Meto promotes S1P secretion/signaling.

219 RIP mediated by site-1 protease (S1P) and site-2 protease (S2P) is involved in proteolyti

220 and are subjected to RIP by site-1 protease (S1P) and site-2 protease (S2P) sequentially in response

221 report that the Arabidopsis SITE-1 PROTEASE (S1P) cleaves endogenous RAPID ALKALINIZATION FACTOR (RAL

222 uires cleavage of SREBP1 by site-1-protease (S1P) and S2P and subsequent translocation into the nucle

223 Together, our data show that the rapid S1P-induced increase in endothelial integrity is mediate

224 ells via the activation of cognate receptors S1P(2) and S1P(3).

225 interacting with its five cognate receptors: S1P(1-5) In this study, using a combination of drug phar

226 that S1P cleaves BBF2H7 just before the RXXL S1P recognition motif.

227 That said, S1P plays pleiotropic roles in the immune response, and

228 support the survival of T cells by secreting S1P via the transporter SPNS2, that this S1P signals thr

229 from S1P(2) We further show that a selective S1P(2) agonist, CYM-5478, reduces allodynia in a rat mod

230 e reveal that abluminal polarization shields S1P(1) from circulating endogenous and synthetic ligands

231 (ERBB2/HER2), which is regulated by the SK1/S1P pathway and is normally not expressed in MCF-7 cells

232 uffice to activate local MC and elevate skin S1P.

233 Furthermore, skin S1P levels remain unchanged in MC-deficient mice exposed

234 y suggest that the development of a specific S1P(2) agonist may represent a promising therapeutic app

235 hate pathway (PPP), along with sphingolipid (S1P) signaling, activates mTOR and allows translation of

236 cate a pivotal regulatory role for the SphK1/S1P axis in maintaining the balance between immunosurvei

237 Surprisingly, S1P had the opposite effect on effector memory T cells,

238 1) These findings demonstrate that sustained S1P(1) activation can occur pharmacologically without co

239 nd its derivative, BAF312, which only target S1P receptors 1 and 5, in a mouse model of cryptococcal

240 Drugs targeting S1P signaling have been remarkably successful in treatme

241 of sphingosine-1-phosphate (S1P) and targets S1P receptors 1, 3, 4, and 5.

242 ectrophysiological recordings confirmed that S1P evoked action potential (AP) generation in a concent

243 tructure at 1.9 A resolution deciphered that S1P binds to the surface of 2,3-BPG-deoxyHbA and causes

244 Cell-based assays demonstrate that S1P can rapidly up-regulate the expression of SNAI2 in b

245 In this study, we demonstrated that S1P cleaves BBF2H7 just before the RXXL S1P recognition

246 Here, we demonstrated that S1P metabolism is significantly disrupted in HD even at

247 We next found that S1P effectively could reverse alcohol-induced endothelia

248 We found that S1P in the lungs strongly activated 81.5% of nodose fibr

249 Interestingly, in this study, we found that S1P synthesized by an isoform of sphingosine kinase (SPH

250 These results support the hypothesis that S1P may play a role in evoking C-fibre-mediated airway s

251 Lastly, we observed that S1P administration ameliorated hypotension and microvasc

252 Functional studies revealed that S1P and 2,3-BPG work synergistically to decrease both Hb

253 Here we show that S1P is essential not only for the circulation of naive T

254 , vascular transcriptome analysis shows that S1P pathway is critical in the regulation of vascular fu

255 Our results suggest that S1P and SphK2 in the nucleus are linked to the regulatio

256 Taken together, our findings suggest that S1P produced by SPHK1 induces SNAI2 expression via S1P(2

257 in lymphocyte recirculation and suggest that S1P promotes retention of memory T cell subsets in secon

258 Knockdown studies suggest that S1P(2) and S1P(3) mediate this effect by activating myoc

259 The S1P and apo M content of isolated HDL particles strongly

260 The S1P receptor 1 agonist SEW2871 rapidly normalized parace

261 The S1P signalling pathway is being targeted therapeutically

262 eficiency in sphingosine kinase (SphK)1, the S1P-producing enzyme, or in MC, remarkably mitigates all

263 uropathic pain by selectively activating the S1P receptor subtype 1 (S1PR1) in astrocytes.

264 peptide (BSP) fragments located between the S1P and S2P cleavage sites in cells exposed to ER stress

265 g nodose neurons express mRNA coding for the S1P receptor S1PR3.

266 C-fibre neurons express mRNA coding for the S1P receptor S1PR3.

267 Mice given the S1P antagonist (FTY720) with HSCs had increased hepatic

268 However, the S1P degradation-incompetent form of SPL also enhanced IF

269 INS1E cells by genetically manipulating the S1P-metabolizing enzyme S1P lyase (SPL).

270 sses the cellular and molecular basis of the S1P gradients and aims to interpret its physiological si

271 that expression of SPNS2, expression of the S1P receptor S1PR5 on NK cells, and expression of the ch

272 deficiency in S1P production, export, or the S1P(1) receptor substantially exacerbates brain injury i

273 to highlight the potential of targeting the S1P axis towards development of non-narcotic therapeutic

274 We have shown previously that the S1P receptor agonist fingolimod (FTY720) attenuates psyc

275 y cords than in the T cell zone and that the S1P transporter SPNS2 on lymphatic endothelial cells gen

276 We propose that the S1P-S1PR axis in keratinocytes works as a biosensor for

277 ingosine-1-phosphate (S1P) signaling via the S1P receptor 1 (S1PR1) in the vascular endothelial cells

278 cells from C57BL6 mice, with or without the S1P antagonist FTY720; we then studied HSC mobilization

279 l TNF(+) T and Th17 cells and increase their S1P-receptor-1 mediated egress from the intestine and re

280 ovel role for Abl kinases in mediating these S1P effects.

281 ing S1P via the transporter SPNS2, that this S1P signals through S1P1R on T cells, and that the requi

282 lmonary system, T(RM) are identified through S1P antagonist CD69 and expression of integrins CD103/be

283 binding to the following 5 GPCRs: S1P(1) to S1P(5).

284 t as ceramides, but cannot be metabolized to S1P.

285 s study, we assessed the ex vivo response to S1P of primary human T cell subsets.

286 but not blood leukocytes were responsive to S1P gradients, suggesting that T cell responsiveness is

287 We also measured total S1P by liquid chromatography-mass spectrometry and isola

288 gulator KLF-2, and reduced chemotaxis toward S1P and CCL21.

289 In contrast, a clinically used S1P(1) functional antagonist, siponimod, conferred minim

290 s, keratinocytes communicate damage by using S1P release and tight control of S1PR1 and 2.

291 ulfate, LOX, FAK1), cell cycle genes (USP16, S1P complexes), and DNA damage repair genes.

292 (S1P), ERK1/2 and matriptase activation via S1P receptor 4 (S1PR4).

293 S1P regulates diverse cell activities via S1P receptors (S1PRs).

294 FTY720 triggers MDSCs to release GM-CSF via S1P receptor 3 (S1pr3) through Rho kinase and extracellu

295 oduced by SPHK1 induces SNAI2 expression via S1P(2)-YAP and S1P(3)-MRTF-A pathways, leading to enhanc

296 , and cell-based assays, we examined whether S1P signaling may represent a potential target in the tr

297 his study reveals a novel mechanism by which S1P activates parallel pathways that regulate the expres

298 ultiple cytoskeletal changes associated with S1P-mediated endothelial barrier enhancement and suggest

299 of normal human epidermal keratinocytes with S1P increased the expressions of IL36G, TNFA, and IL8, b

300 n the ganglia during tracheal perfusion with S1P (10 muM).