ライフサイエンスコーパス: EPCR

1 EPCR and EPCR-bound ligands were endocytosed rapidly via

2 EPCR and its ligand APC promote cell survival that contr

3 EPCR exhibits a sequence and three-dimensional homology

4 EPCR is a major histocompatibility complex-like molecule

5 EPCR is detected in the giant trophoblast cells at the f

6 EPCR plays a crucial role in the protein C anticoagulant

7 EPCR structure contains a hydrophobic groove filled with

8 EPCR(R84A/R84A) mice are viable and reproduce normally.

9 EPCR(R84A/R84A) mice challenged with lipopolysaccharide

10 EPCR-blocking antibody (RCR-252) significantly attenuate

11 EPCR-dependent protein C activation and APC antiapoptoti

12 EPCR-mediated FVIIa endocytosis/recycling also resulted

13 EPCR/APC is a novel target of relevance in the clinical

14 abundance of parasite PfEMP1 DC8 and group A EPCR-binding domains.

15 Ad.EPCR treatment elicited recruitment of macrophages and N

16 Ad.EPCR treatment resulted in a marked increase in tumor ce

17 Intrapleural injection of Ad.EPCR into mice with an established MPM originating from

18 dependent of PC interaction, we generated an EPCR point mutation knock-in mouse (EPCR(R84A/R84A)) whi

19 may include the inhibition of NETosis in an EPCR-, PAR3-, and Mac-1-dependent manner, providing addi

20 new paradigm for understanding how PAR-1 and EPCR participate in protective signaling events in endot

21 e PfEMP1s, predicted to bind both ICAM-1 and EPCR, is associated with increased risk of developing ce

22 critical for its anticoagulant activity and EPCR-dependent barrier protection, had no effect on its

23 cause mFVIIa-FMR models the TF-dependent and EPCR binding properties of rhFVIIa, our data unmask a no

24 nding to EPCR promotes EPCR endocytosis, and EPCR-mediated endocytosis may facilitate the transcytosi

25 EPCR and EPCR-bound ligands were endocytosed rapidly via a dynami

26 Our study reveals new roles for PAR1 and EPCR in controlling NO production to balance maintenance

27 Tie2 activation by FXa required PAR3 and EPCR.

28 oth protein C activation (thrombomodulin and EPCR) and APC cellular signaling (EPCR and PAR-1) pathwa

29 crease in PC activation not seen when TM and EPCR are anchored to distinct cell adhesion molecules.

30 e pattern with VWF (paired t test for TM and EPCR, each P < .001; for VWF, P = .01).

31 APC-mediated [Ca2+]i signaling, whereas anti-EPCR antibody RCR92 that does not block APC binding did

32 orylation of Dab1 and GSK3beta, whereas anti-EPCR or anti-PAR1 blocking antibodies did not.

33 a required the enzymatic active site of APC, EPCR, and PAR-1, highlighting a key role for APC's cytop

34 Inhibition of NO production by aPC-EPCR-PAR1 signaling reduces progenitor cell egress from

35 silencing of EPCR expression or blocking APC/EPCR interaction reduced infiltration in the target orga

36 Signaling pathway triggered by APC/EPCR and its relevance in apoptosis was studied in vitro

37 mL) can also induce microparticle-associated EPCR release to a similar extent as APC (100 nM), it is

38 Based on our findings, we believe EPCR represents the first known marker that 'explicitly'

39 n studies demonstrate an interaction between EPCR and S1P1 upon APC treatment.

40 se results suggest that a cross-talk between EPCR and an unknown FX/FXa receptor, which does not requ

41 an prothrombin Gla domain, which cannot bind EPCR or support protein S cofactor activity, has 22/45 r

42 hrocyte membrane protein 1) family that bind EPCR, including DC8 var genes that have previously been

43 th cerebral malaria were more likely to bind EPCR and ICAM-1 than IE from children with uncomplicated

44 esidue variant, PC(PT8), also failed to bind EPCR.

45 iduals in malaria-endemic regions that block EPCR binding of diverse CIDRalpha1 variants.

46 However, the V(gamma)4V(delta)5 TCR bound EPCR independently of lipids, in an antibody-like way.

47 ing by activated protein C through PAR1, but EPCR may have additional roles by interacting with the 4

48 e impairment of the thrombomodulin-protein C-EPCR anticoagulation pathway.

49 st to other stem cell markers, such as CD38, EPCR expression is maintained when cells are introduced

50 CHO-EPCR cells and human umbilical vein endothelial cells (H

51 We combine crystal structures of CIDRalpha1:EPCR complexes with analysis of 885 CIDRalpha1 sequences

52 Conversely, EPCR expression in the embryo, without expression in the

53 In the last decade, EPCR has received wide attention after it was discovered

54 To prevent this fibrin deposition, EPCR(+/-)-crossed female mice received a daily subcutane

55 critical target of aPC therapy, and document EPCR-independent antiinflammatory effects of aPC on inna

56 . (2015) explore how diverse PfEMP1s embrace EPCR, promoting parasite survival and killing African ch

57 We examined EPCR levels using a microarray dataset of 107 patients.

58 oth muscle cells that constitutively express EPCR and TF, thrombin and FVIIa/FX but not FVIIa alone i

59 These cells, which normally express EPCR, are in direct contact with the maternal circulatio

60 on in nonaggressive MPM cells that expressed EPCR and PAR1 with minimal levels of tissue factor did n

61 hat mice implanted with MPM cells expressing EPCR had elevated levels of IFNgamma and TNFalpha compar

62 These findings show that extraembryonic EPCR expression is critical for embryo development.

63 s from E13.5, suggesting that extraembryonic EPCR expression may be essential for embryonic viability

64 PM cells that lack or express tissue factor, EPCR or PAR1, and an orthotopic nude mouse model of MPM.

65 udies also discovered additional ligands for EPCR, which include factor VIIa, Plasmodium falciparum e

66 s provide novel insights into mechanisms for EPCR multifunctionality.

67 confirming Leu-8 as the critical residue for EPCR recognition.

68 These data reveal an essential role for EPCR and PAR1 on hematopoietic cells, identify EPCR-expr

69 BM transplant experiments suggest a role for EPCR on hematopoietic stem cells and BM stromal cells in

70 hese findings suggest a detrimental role for EPCR-binding CIDRalpha1 domains in brain swelling.

71 Potential roles for EPCR in hematopoiesis are suggested by the finding that

72 observations open unsuspected new roles for EPCR in hemostasis, malaria pathogenesis, innate immunit

73 Genotyping of progeny obtained from EPCR(+/-) interbreeding indicated that EPCR(-/-) embryos

74 Ia), and intracellular trafficking of FVIIa, EPCR, and Rab proteins was evaluated by immunofluorescen

75 ysiological importance of EPCR, we generated EPCR-deficient mice by homologous targeting in embryonic

76 ld-type mice into animals with hematopoietic EPCR deficiency restored the therapeutic efficacy of aPC

77 les showed a robust association between high EPCR levels and poor prognosis, particularly in stage I

78 tumor growth through PAR1, and they show how EPCR can attenuate the growth of tissue factor-expressin

79 he biochemical level, it remains unclear how EPCR interaction with its ligands at the cell surface im

80 Understanding how EPCR-APC induces cytoprotective effects through activati

81 (DH) site mapping across 38 kb of the human EPCR gene (hEPCR) locus identified 3 potential regulator

82 CR and PAR1 on hematopoietic cells, identify EPCR-expressing dendritic immune cells as a critical tar

83 together, our studies suggest that impaired EPCR/PC-binding interactions not only result in procoagu

84 importance of EPCR has been demonstrated in EPCR knockout mice which show early embryonic lethality

85 aria isolates had substantial differences in EPCR binding affinity and blockade activity for its liga

86 in intron 2, was primarily hypersensitive in EPCR-negative cells, and capable of initiating antisense

87 PCh in EPCR could be exchanged for lysophosphatidylcholine (lys

88 lished whether lipid exchange takes place in EPCR as a regulatory mechanism of its activity.

89 ponses to endotoxin increase with increasing EPCR expression.

90 Interestingly, EPCR(R84A/R84A) mice develop splenomegaly as a result of

91 motes tumor cell apoptosis, and intrapleural EPCR gene therapy suppresses MPM progression.

92 xpressing tissue factor and PAR1 but lacking EPCR and PAR2 (F2RL1) generated large tumors in the pleu

93 ished MPM originating from MPM cells lacking EPCR reduced the progression of tumor growth.

94 red to mice implanted with MPM cells lacking EPCR.

95 to in vivo challenge with LPS, mice lacking EPCR or PAR2 failed to fully initiate an interferon-regu

96 released microparticle bound is full-length EPCR (49 kDa) and APC retains factor V-inactivating acti

97 ated mice in which one allele of full-length EPCR was replaced by sEPCR (Procrs/+).

98 , increases retention of bone marrow NO(low) EPCR(+) LT-HSCs and protects mice from chemotherapy-indu

99 its structure suggests a role in maintaining EPCR structure rather than contributing directly to prot

100 e maintenance and recruitment of bone marrow EPCR(+) LT-HSCs, with potential clinical relevance for s

101 It is unknown whether membrane EPCR (mEPCR) heterozygosity and/or physiologically eleva

102 logous to rhFVIIa, but binds poorly to mouse EPCR (mEPCR).

103 rated an EPCR point mutation knock-in mouse (EPCR(R84A/R84A)) which lacks the ability to bind PC/APC.

104 these domains mimic features of the natural EPCR ligand and can block this ligand interaction.

105 , PC(PT8/10) (L8V/H10K) displayed negligible EPCR affinity, despite normal binding to anionic phospho

106 stational lethality, this regimen yielded no EPCR(-/-) pups.

107 D11b, PAR1, or sphingosine kinase-1, but not EPCR, abolished the ability of APC to suppress the macro

108 revealed that the expression of TM, but not EPCR, was reduced significantly early after graft implan

109 These data suggest that novel EPCR ligation and S1P1 transactivation results in EC cyt

110 Bone marrow cells isolated on the basis of EPCR expression alone are highly enriched for hematopoie

111 nd subsequently fractionated on the basis of EPCR expression indicates that stem cell activity is alw

112 oparticle formation and antibody blockade of EPCR or PAR1 cleavage and activation abrogates this APC

113 vivo studies in mice showed that blockade of EPCR with EPCR-blocking antibodies impaired the early ph

114 Thus, the colocalization of EPCR and PAR-1 in lipid rafts is a key requirement for t

115 multimolecular stress signature composed of EPCR and costimulatory ligand(s).

116 IIa, our data unmask a novel contribution of EPCR on the action of rhFVIIa administration in hemophil

117 ke model of mice with a severe deficiency of EPCR.

118 Complete deletion of EPCR function results in embryonic death, at least in pa

119 ild-type CD11chi dendritic cells depleted of EPCR+ cells did not.

120 Malaria-associated depletion of EPCR, with subsequent impairment of the protein C system

121 h endothelial cells leads to dissociation of EPCR from caveolin-1 and recruitment of PAR-1 to a prote

122 negative Rab5A inhibited the endocytosis of EPCR-FVIIa.

123 Here, we show that expression of EPCR and PAR1 on hematopoietic cells is required in mice

124 found significantly increased expression of EPCR and TM in the valvular sinus endothelium as opposed

125 More importantly, ectopic expression of EPCR in aggressive MPM cells attenuated their growth pot

126 Expression of EPCR in mature murine immune cells was limited to a subs

127 Heterologous expression of EPCR promoted PAR1 and PAR2 cleavage by FXa in the terna

128 Previously, a soluble form of EPCR (sEPCR) in human plasma was characterized, and seve

129 A small fraction of EPCR is also localized intracellularly in the recycling

130 is not sensitive to the cofactor function of EPCR.

131 malaria, and indicate that low impairment of EPCR function may contribute to parasite virulence.

132 The physiological importance of EPCR has been demonstrated in EPCR knockout mice which s

133 To determine the physiological importance of EPCR, we generated EPCR-deficient mice by homologous tar

134 conventional dendritic cells independent of EPCR and suppressed IFN-gamma production by natural kill

135 rough the activation of PAR-2 independent of EPCR mobilization.

136 dels of TF signaling, antibody inhibition of EPCR selectively blocked PAR activation by the ternary T

137 that complementary receptor interactions of EPCR binding PfEMP1with ICAM-1 amplifies development of

138 ding to EPCR promoted the internalization of EPCR.

139 ed, cells with genetically reduced levels of EPCR no longer showed a signaling response to the ternar

140 s microvessels, we demonstrated that loss of EPCR and TM at sites of IE cytoadherence is detectible i

141 CM showed cerebral fibrin clots and loss of EPCR, colocalized with sequestered IEs.

142 croscopy studies revealed that a majority of EPCR is localized on the cell surface in membrane microd

143 lipid exchange as a regulatory mechanism of EPCR activity driven by the endothelially expressed secr

144 Because of the pleiotropic nature of EPCR and TM, these data implicate disruption of the endo

145 Although engineered overexpression of EPCR fails to reproduce the effects of UM171 on HSC acti

146 Moreover, overexpression of EPCR induced an increased metastatic activity to target

147 ted and endothelial cells in the presence of EPCR.

148 hibited the barrier-protective properties of EPCR in human brain endothelial cells in vitro.

149 APC (6.25-100 nM) results in the release of EPCR-containing microparticles, as demonstrated by confo

150 , available data suggest a potential role of EPCR in hematopoiesis, autoimmunity, and the control of

151 edly expand our understanding of the role of EPCR in normal physiology and disease, as well as provid

152 provided conflicting data about the role of EPCR in SM.

153 In order to study the role of EPCR independent of PC interaction, we generated an EPCR

154 These results underpin the significance of EPCR binding in pediatric malaria patients that require

155 In vivo, silencing of EPCR expression or blocking APC/EPCR interaction reduced

156 GTPases in the intracellular trafficking of EPCR and FVIIa.

157 the cellular localization and trafficking of EPCR in endothelial cells and a heterologous expression

158 rnalization and intracellular trafficking of EPCR-FVIIa.

159 apeutic efficacy of aPC, whereas transfer of EPCR-deficient CD11chi dendritic cells or wild-type CD11

160 Comprehensive understanding of EPCR may lead to development of novel therapeutic modali

161 y in severe sepsis is predominantly based on EPCR- and PAR1-dependent cell signaling, and APC variant

162 f antibodies against PAR-1, PAR-2, PAR-3, or EPCR.

163 strictly required for PL membrane binding or EPCR recognition.

164 otic challenge with factor Xa/phospholipids, EPCR(R84A/R84A) mice generate more thrombin, less APC, a

165 of endothelial protein C receptor-positive (EPCR(+)) LT-HSCs in the bone marrow and their recruitmen

166 should be mimicked in immunogens to prevent EPCR binding.

167 we found that the protein C receptor (ProcR; EPCR) was required for the normal in vivo and in vitro i

168 activated protein C binding to EPCR promotes EPCR endocytosis, and EPCR-mediated endocytosis may faci

169 We next observed rapid, EPCR and PI 3-kinase-dependent, APC-mediated phosphoryla

170 e binding to endothelial protein C receptor (EPCR) and cleavage of protease activated receptor-1 (PAR

171 require the endothelial protein C receptor (EPCR) and protease activated receptor 1 (PAR1).

172 eptors, endothelial cell protein C receptor (EPCR) and protease-activated receptor 1 (PAR1).

173 tro required endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1), as did

174 talk between endothelial protein C receptor (EPCR) and S1P1, the receptors for APC and S1P, respectiv

175 ding to endothelial cell protein C receptor (EPCR) and subsequent protease activated receptor (PAR)-1

176 lin (TM) and endothelial protein C receptor (EPCR) and that low constitutive expression of these regu

177 egulation of endothelial protein C receptor (EPCR) and thrombomodulin protein expressions, inhibited

178 The endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium fa

179 The endothelial cell protein C receptor (EPCR) augments protein C activation by the thrombin-thro

180 dies to endothelial cell protein C receptor (EPCR) blocked effectively (125)I-FVIIa binding to HUVEC.

181 occupancy of endothelial protein C receptor (EPCR) by the Gla-domain of protein C/APC is responsible

182 The endothelial protein C receptor (EPCR) confers anti-inflammatory properties when bound by

183 sion of endothelial cell protein C receptor (EPCR) in MPM cells suppresses tumorigenicity.

184 f PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria.

185 e binding to endothelial protein C receptor (EPCR) is associated with severe disease has suggested ne

186 The endothelial protein C receptor (EPCR) is crucial for signaling by activated protein C th

187 The endothelial cell protein C receptor (EPCR) is expressed by endothelial cells of large blood v

188 ow that endothelial cell protein C receptor (EPCR) is specifically expressed by mouse CD8+ dendritic

189 otein C with endothelial protein C receptor (EPCR) leads to dissociation of the receptor from caveoli

190 The endothelial protein C receptor (EPCR) limits thrombus formation by enhancing activation

191 Loss of endothelial protein C receptor (EPCR) occurs at the sites of Plasmodium falciparum-infec

192 loss of the endothelial protein C receptor (EPCR) on brain vessels, caused by cytoadherent infected

193 APC) to endothelial cell protein C receptor (EPCR) on endothelial cells.

194 t for either endothelial protein C receptor (EPCR) or PAR1 revealed that the EPCR-dependent signaling

195 The endothelial cell protein C receptor (EPCR) plays a critical role in augmenting protein C acti

196 The endothelial protein C receptor (EPCR) plays an important role in cardiovascular disease

197 e shown that endothelial protein C receptor (EPCR) polymorphisms and soluble EPCR levels are associat

198 mechanism of endothelial protein C receptor (EPCR) release that is not inhibited by metalloproteinase

199 The endothelial cell protein C receptor (EPCR) shares approximately 20% sequence identity with th

200 vel APC-endothelial cell protein C receptor (EPCR) signaling pathway in endothelial cells.

201 cts with the endothelial protein C receptor (EPCR) through its gamma-carboxyglutamic acid (Gla) domai

202 ding of endothelial cell protein C receptor (EPCR) to its ligands is well characterized at the bioche

203 Endothelial cell protein C receptor (EPCR) was first identified and isolated as a cellular re

204 to the endothelial cell protein C receptor (EPCR), a cellular receptor for protein C and activated p

205 lates impair endothelial protein C receptor (EPCR), a protein involved in coagulation and endothelial

206 nteract with endothelial protein C receptor (EPCR), allowing infected erythrocytes to synergistically

207 for soluble endothelial protein C receptor (EPCR), as demonstrated by surface plasmon resonance stud

208 lin (TM) and endothelial protein C receptor (EPCR), endothelial membrane proteins that partner in act

209 g the murine endothelial protein C receptor (EPCR), is expressed at high levels within the bone marro

210 suggest the endothelial protein C receptor (EPCR), known for its pivotal role in mediating cytoprote

211 require the endothelial protein C receptor (EPCR), protease-activated receptor (PAR) 1, and PAR3.

212 il receptors endothelial protein C receptor (EPCR), protease-activated receptor 3 (PAR3), and macroph

213 e quantified endothelial protein C receptor (EPCR), thrombomodulin (TM), and von Willebrand factor (V

214 rectly bound endothelial protein C receptor (EPCR), which allowed gammadelta T cells to recognize bot

215 pts encoding endothelial protein C receptor (EPCR)-binding domains, in combination with high parasite

216 through the endothelial protein C receptor (EPCR)-dependent cleavage of protease-activated receptor

217 through its endothelial protein C receptor (EPCR)-dependent cleavage of protease-activated receptor

218 (APC) exerts endothelial protein C receptor (EPCR)-dependent neuroprotective effects in a brain focal

219 to the endothelial cell protein C receptor (EPCR).

220 , but not on endothelial protein C receptor (EPCR).

221 and the endothelial cell protein C receptor (EPCR).

222 nding to the endothelial protein C receptor (EPCR).

223 ICAM-1), and endothelial protein C receptor (EPCR); however, cytoadhesion patterns typical for pediat

224 factor, endothelial cell protein C receptor (EPCR, PROCR), and protease activated receptor-1 (PAR1, F

225 ells express endothelial protein C receptor (EPCR/CD201/PROCR) when exposed to the hematopoietic stem

226 1 (PAR1) and endothelial protein C receptor (EPCR; also known as Procr).

227 ein C (PC) with the endothelial PC receptor (EPCR) enhances activated PC (APC) generation.

228 naling and the endothelial cell PC receptor (EPCR) prevented vascular leakage, and pharmacologic or g

229 or-alpha converting enzyme activity, reduced EPCR shedding, and restored plasma protein C level.

230 with activated protein C (aPC) that retains EPCR(+) LT-HSCs by limiting NO generation, reducing Cdc4

231 scFv/TM and scFv/EPCR bound to mouse endothelial PECAM-1 with high affini

232 Like the CD1 series, EPCR has a lipid in the corresponding groove.

233 odulin and EPCR) and APC cellular signaling (EPCR and PAR-1) pathways are colocalized in the membrane

234 -dependent and requires the APC active site, EPCR, and protease activated receptor 1 (PAR1) on endoth

235 C receptor (EPCR) polymorphisms and soluble EPCR levels are associated with thrombotic diseases.

236 a, which also possesses Leu-8, bound soluble EPCR with similar affinity to wild-type protein C, colle

237 pite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies

238 he major phospholipid bound to human soluble EPCR (sEPCR).

239 ationships between endogenous plasma soluble EPCR (sEPCR) levels and clinical presentation or mortali

240 Here we show that soluble EPCR regulates the interaction of FX with human or mouse

241 Although some EPCR(-/-) embryos were rescued from midgestational letha

242 These results demonstrate that EPCR interacts with the ternary TF coagulation initiatio

243 In this study, we demonstrate that EPCR is associated with caveolin-1 in lipid rafts of end

244 We demonstrate that EPCR occupancy recruits G-protein coupled receptor kinas

245 In vitro studies demonstrated that EPCR expression renders MPM cells highly susceptible to

246 resent data provide convincing evidence that EPCR serves as a cellular binding site for FVII/FVIIa.

247 atopoiesis are suggested by the finding that EPCR is located on hematopoietic stem cells at reasonabl

248 Altogether, our results indicate that EPCR is a reliable and cell culture-compatible marker of

249 from EPCR(+/-) interbreeding indicated that EPCR(-/-) embryos died on or before embryonic day 10.5 (

250 Immunohistochemical analyses revealed that EPCR expression in tumor cells reduced tumor cell prolif

251 thrombin infusion experiments revealed that EPCR heterozygosity (Procr+/-) impaired protein C activa

252 ansfected with PAR1 constructs revealed that EPCR occupancy initiates beta-arrestin-2 biased PAR1 sig

253 In summary, our data show that EPCR expression in MPM cells promotes tumor cell apoptos

254 In this article, we show that EPCR-positive UM171-treated cells, as opposed to EPCR-ne

255 main and dose titrations with FX showed that EPCR interacted primarily with FX to attenuate FX activa

256 structure and the lipid antigen suggest that EPCR may be involved in preventing autoimmunity, which w

257 lex to enable PAR signaling and suggest that EPCR may play a role in regulating the biology of TF-exp

258 in can also recruit thrombin to activate the EPCR-bound protein C, thereby eliciting PAR-1 signaling

259 iation complex of blood coagulation, and the EPCR-dependent activation of protease-activated receptor

260 Deletion of the EPCR gene (Procr) in mice leads to embryonic lethality b

261 ons of FVIIa were found to impair partly the EPCR-dependent protein C activation and APC-mediated cel

262 f 885 CIDRalpha1 sequences, showing that the EPCR-binding surfaces of CIDRalpha1 domains are conserve

263 C receptor (EPCR) or PAR1 revealed that the EPCR-dependent signaling activity of APC is primarily re

264 an be therapeutically protective through the EPCR-PAR1 signaling despite ongoing thrombin generation

265 Using peptides corresponding to the EPCR-binding region, antibodies can be purified from ind

266 en inhibits the host immune response via the EPCR.

267 When the EPCR was blocked, F. tularensis lost the ability to supp

268 d the binding affinities of protein C/APC to EPCR.

269 rain endothelium and in HUVECs by binding to EPCR and signaling via PAR-1.

270 Antibody RCR252 that ablates APC binding to EPCR blocked APC-mediated [Ca2+]i signaling, whereas ant

271 FVIIa binding to EPCR failed to accelerate FVIIa activation of factor X o

272 FVIIa binding to EPCR is confirmed by demonstrating a marked increase in

273 FVIIa binding to EPCR may promote the endocytosis of this receptor/ligand

274 t study, we show that FVIIa, upon binding to EPCR on endothelial cells, activates endogenous protease

275 Ia (FVIIa) or activated protein C binding to EPCR promoted the internalization of EPCR.

276 that FVIIa or activated protein C binding to EPCR promotes EPCR endocytosis, and EPCR-mediated endocy

277 The effects of APC binding to EPCR rapidly triggered Akt and extracellular signal-regu

278 FVIIa binding to EPCR was shown to facilitate FVIIa endocytosis.

279 in protein C/APC that favor their binding to EPCR.

280 nsequences and relevance of FVIIa binding to EPCR.

281 as competitive inhibitors for APC binding to EPCR.

282 nt data provide evidence that FVIIa bound to EPCR on endothelial cells activates PAR1-mediated cell s

283 in C, and activated protein C (APC) bound to EPCR with similar affinity.

284 inflammatory activity is likely to be due to EPCR's interactions with the integrin Mac-1 (CD11b/CD18)

285 ces nitric oxide (NO) production, leading to EPCR shedding mediated by tumor necrosis factor-alpha-co

286 -positive UM171-treated cells, as opposed to EPCR-negative cells, exhibit robust multilineage repopul

287 in human brain endothelial cells (BECs) via EPCR and PAR-1.

288 direct effects of APC on cultured cells via EPCR and PAR-1.

289 FVIIa-induced, barrier-protective effect was EPCR dependent and did not involve PAR2.

290 Thus, when EPCR is bound by protein C, the PAR-1 cleavage-dependent

291 structures beneath the plasma membrane where EPCR and FVIIa accumulated.

292 s attenuated their growth potential, whereas EPCR silencing in nonaggressive MPM cells engineered to

293 resses MPM tumor growth and evaluate whether EPCR gene therapy could suppress the progression of MPM

294 Here, we study whether EPCR facilitates rhFVIIa hemostasis in hemophilia using

295 aimed to investigate the mechanism by which EPCR suppresses MPM tumor growth and evaluate whether EP

296 stem cell activity is always associated with EPCR-expressing cells.

297 -induced expression of TF and crosstalk with EPCR, PAR2, and TLR4 therefore appear necessary for the

298 emonstrate that Procr-deficient embryos with EPCR expression on placenta giant trophoblasts can be ca

299 es in mice showed that blockade of EPCR with EPCR-blocking antibodies impaired the early phase of FVI

300 cells that had been stably transfected with EPCR compared with the wild-type.