ライフサイエンスコーパス: VEGFR-3

1 rg(108)) is critical for binding VEGFR-2 and VEGFR-3.

2 sions and affected colocalization of FAK and VEGFR-3.

3 ve shown the physical association of FAK and VEGFR-3.

4 VEGF receptor (VEGFR)-1, but not VEGFR-2 or VEGFR-3.

5 PI3K activator prevented the effects of anti-VEGFR-3.

6 t Src family kinases are upstream of PKC and VEGFR-3.

7 ired for H(2)O(2)-induced phosphorylation of VEGFR-3.

8 healthy adult blood donors are positive for VEGFR-3.

9 imilar degree of tyrosine phosphorylation of VEGFR-3.

10 helial receptor tyrosine kinases VEGFR-2 and VEGFR-3.

11 nism involving signaling of both VEGFR-2 and VEGFR-3.

12 ermal macrophages themselves did not express VEGFR-3.

13 different growth factor receptors, including VEGFR-3.

14 EC-expressed growth factor receptors such as VEGFR-3.

15 inase 1/2 (ERK1/2), a downstream effector of VEGFR-3.

16 ynthesis and promoted protein degradation of VEGFR-3.

17 Anti-VEGFR-3 abolished CCL21 gradients around lymphatics, alt

18 cells resulted in the formation of adherent VEGFR-3(+)Ac-LDL(+) (Ac-LDL = acetylated low-density lip

19 Normally, VEGFR-3 activates Akt signaling in lymphatic endothelial

20 provide direct evidence for the key role of VEGFR-3 activation in metastasis.

21 Inhibition of VEGFR-3 activation more potently suppressed regional and

22 eraction (Arg737) compromised VEGF-C induced VEGFR-3 activation.

23 scular endothelial growth factor receptor 3 (VEGFR-3) ameliorated aGVHD and improved survival in muri

24 re ECs do not express CD133, coexpression of VEGFR-3 and CD133 on CD34(+) cells identifies a unique p

25 f (1) inhibiting the biochemical function of VEGFR-3 and FAK, (2) inhibiting proliferation of a diver

26 he protein-protein interface between FAK and VEGFR-3 and identified compound C4 (chloropyramine hydro

27 O(2) induced the tyrosine phosphorylation of VEGFR-3 and its association with the signaling adaptor p

28 een beta(1) integrin and VEGFR-3 in both 293/VEGFR-3 and primary DMEC cells.

29 Here, we identified VEGFR-3 and Prox1 as downstream targets of the NF-kappaB

30 ssion of lymphatic specific genes, including VEGFR-3 and Prox1.

31 s VEGF-C, thereby blocking signaling through VEGFR-3 and suppressing lymphangiogenesis induced by VEG

32 was down-regulated around lymphatics by anti-VEGFR-3 and this was dependent on heparanase-mediated de

33 The VEGF-C/VEGFR-3 and VEGF-A/VEGF-R2 signaling pathways are two of

34 trate, for the first time, the expression of VEGFR-3 and VEGF-C on tissue DC, which implicate a novel

35 Both VEGFR-3 and VEGFR-2 were involved in corneal suture-indu

36 zed to receive intraperitoneal injections of VEGFR-3 and VLA-1-neutralizing antibodies or their contr

37 placental growth factor (PlGF), VEGFR-1, and VEGFR-3 and, at term, VEGF-A, PlGF, and VEGFR-1.

38 Neutralizing antibodies against VEGFR-3 and/or VEGFR-2 were administrated systemically w

39 scular endothelial growth factor receptor 3 (VEGFR-3) and podoplanin.

40 scular endothelial growth factor receptor-3 (VEGFR-3) and Prox1.

41 ced 68% by blocking VEGFR-2, 83% by blocking VEGFR-3, and 99% by blocking both receptors.

42 growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and c-kit.

43 elial growth factor C (VEGF-C), its receptor VEGFR-3, and lymphangiogenesis during development of exp

44 a VEGF-C/-D/VEGFR-3-independent pathway as a VEGFR-3 antagonist selectively inhibited VEGF-C-induced,

45 Systemic treatment with either VEGFR-2 or VEGFR-3 antagonistic antibodies suppressed tumor lymphan

46 The administration of anti-VEGFR-3 antibodies did not interfere with hematopoietic

47 ion treatment with the anti-VEGFR-2 and anti-VEGFR-3 antibodies more potently decreased lymph node an

48 scular endothelial growth factor receptor 3 (VEGFR-3) antibody to block lymphangiogenesis in mice.

49 that signals from both beta(1) integrin and VEGFR-3 are required for this cell function.

50 scular endothelial growth factor receptor-3 (VEGFR-3) are protein tyrosine kinases that are overexpre

51 scular endothelial growth factor receptor 3 (VEGFR-3) are the major lymphatic growth factor and recep

52 genic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development.

53 ke phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis,

54 ox 1-enhanced green fluorescence protein and VEGFR-3 as markers.

55 Overexpression of VEGFR-3 attenuated CPX inhibition of ERK1/2 phosphorylat

56 ness of preexisting lymphatic endothelium to VEGFR-3 binding factors, VEGF-C and VEGF-D, ultimately r

57 156S, a mutant form of VEGF-C with selective VEGFR-3 binding, alleviates an established rejection res

58 In addition, in the VEGFR-3 blockade group, the percent reduction of HA is s

59 plantation of an 80-ng bFGF micropellet with VEGFR-3 blockade.

60 Phe(93) to Thr(98), is required for binding VEGFR-3 but not VEGFR-2.

61 xpression of podoplanin and VEGF receptor 3 (VEGFR-3) but not of LYVE-1 and prospero homeobox protein

62 During contact hypersensitivity, VEGFR-3, CCL21, and HS expression were all attenuated, a

63 By comparison, VEGFR-3, CD31, and CD105 had decreases in the range of 2

64 Analysis of the human VEGFR-3 cDNA and genomic sequence reveals that these two

65 CD34(+)VEGFR-3(+) cells from fetal liver coexpress the stem/pre

66 Incubation of isolated CD34(+)VEGFR-3(+) cells in EC growth medium resulted in a stron

67 racterized the phenotype and distribution of VEGFR-3(+) cells.

68 feration (40-fold in 2 weeks) of nonadherent VEGFR-3(+) cells.

69 let-derived growth factor receptor beta, and VEGFR-3 cellular receptor autophosphorylation was also o

70 3 (VEGFR-3) expression, as overexpression of VEGFR-3 conferred partial resistance to CPX inhibitory e

71 that human CD34(+)CD133(+) cells expressing VEGFR-3 constitute a phenotypically and functionally dis

72 he association between the NH(2) terminus of VEGFR-3, containing the peptide identified by phage disp

73 interventions that inhibit gB activation of VEGFR-3 could be useful in the treatment of this neoplas

74 A structural model of the VEGF-C/VEGFR-3 D1-7 complex derived from small-angle X-ray scat

75 complex with VEGFR-3 domains D1-2 and of the VEGFR-3 D4-5 homodimer.

76 VEGFR-3(+) DC are CD11c(+)CD45(+)CD11b(+), and are mostl

77 VEGFR-3(+) DC in normal corneas are VEGF-C(-)neuropilin-

78 on, there is rapid increase in the number of VEGFR-3(+) DC in the cornea associated with heightened m

79 A thermodynamic analysis of VEGFR-3 deletion mutants showed that D3, D4-5, and D6-7

80 In vivo, long-term activation or blockade of VEGFR-3 did not affect steady-state murine megakaryopoie

81 Inhibition of VEGFR-2/VEGFR-3 did not prevent the formation of BALT.

82 Interestingly, knockdown of VEGFR-3 does not affect galectin-8-mediated lymphatic en

83 crystal structures of VEGF-C in complex with VEGFR-3 domains D1-2 and of the VEGFR-3 D4-5 homodimer.

84 d whether a combined blockade of VEGFR-2 and VEGFR-3 effectively suppresses early-, middle-, or late-

85 However, the origin of VEGFR-3(+) endothelial cells (ECs) and the mechanisms by

86 inhibited VEGF-C-induced phosphorylation of VEGFR-3, ERK1/2, and AKT.

87 Furthermore, we observed that VEGFR-3 expression and activation enhance KSHV infection

88 blots and immunostaining revealed VEGF-C and VEGFR-3 expression in CNV lesions, mainly in macrophages

89 inflammatory stimuli also elevated Prox1 and VEGFR-3 expression in cultured lymphatic endothelial cel

90 Here we define VEGFR-3 expression in GEnC and investigate the effects o

91 We report that Notch induces VEGFR-3 expression in vitro in human endothelial cells a

92 ity decreased more than 70%, and VEGFR-2 and VEGFR-3 expression was reduced in surviving endothelial

93 del, following local phVEGF-C gene transfer, VEGFR-3 expression was significantly increased.

94 ergizes with the p50 of NF-kappaB to control VEGFR-3 expression.

95 rized by blood vessels that are positive for VEGFR-3 expression.

96 scular endothelial growth factor receptor-3 (VEGFR-3) expression, as overexpression of VEGFR-3 confer

97 VEGF-C and VEGFR-3 expressions were examined with immunohistochemis

98 rol several lineage-specific genes including VEGFR-3, FGFR-3, and neuropilin-1 and is required along

99 urn, interaction of VEGF-C with its receptor VEGFR-3 (FLT-4) promotes leukemia survival and prolifera

100 nases, including VEGFR-1/Flt-1, VEGFR-2/KDR, VEGFR-3/Flt-4, the platelet-derived growth factor recept

101 opment of these vessels depends on Vegfc and VEGFR-3/Flt4 signaling.

102 scular endothelial growth factor receptor 3 (VEGFR-3/FLT4) is a receptor tyrosine kinase that regulat

103 rozygous for null alleles of both Notch1 and VEGFR-3 had significantly reduced viability and displaye

104 Although VEGFR-3 has been linked primarily to the regulation of l

105 Mutations in VEGFR-3 have been identified in patients with primary ly

106 VEGFR-2/VEGFR-3 heterodimers were more abundant in the dilated l

107 red for VEGF-D to drive formation of VEGFR-2/VEGFR-3 heterodimers which have recently been shown to p

108 ), and by inhibition of VEGF-C activity with VEGFR-3-Ig (AdVEGFR-3-Ig).

109 contrast, inhibition of VEGF-C activity with VEGFR-3-Ig inhibited lymphangiogenesis and angiogenesis

110 In response to dermal immunization, K14-VEGFR-3-Ig mice produced lower Ab titers.

111 ll-mediated CHS responses were strong in K14-VEGFR-3-Ig mice, but importantly, their ability to induc

112 tact hypersensitivity (CHS) challenge in K14-VEGFR-3-Ig mice, which lack dermal lymphatic capillaries

113 Functionally, specific activation of VEGFR-3 impaired the transition to polyploidy of CD41+ c

114 act genetically, that Notch directly induces VEGFR-3 in blood endothelial cells to regulate vascular

115 an association between beta(1) integrin and VEGFR-3 in both 293/VEGFR-3 and primary DMEC cells.

116 CLEC14A formed a complex with VEGFR-3 in endothelial cells (ECs), and CLEC14A KO resul

117 tics to target the signaling between FAK and VEGFR-3 in human tumors.

118 the present study, we demonstrate a role for VEGFR-3 in megakaryopoiesis.

119 s strongly, suggesting a regulatory role for VEGFR-3 in megakaryopoiesis.

120 ut not the lymphoedema-linked mutant form of VEGFR-3 in porcine artery endothelial cells significantl

121 However, activation of VEGFR-3 in sublethally irradiated mice resulted in signi

122 in the increased tyrosine phosphorylation of VEGFR-3 in the absence of a cognate ligand.

123 GEnC expressed VEGFR-3 in tissue sections and culture, and VEGF-C incre

124 the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice.

125 Moreover, activation of VEGFR-3 increased platelet counts in thrombopoietin-trea

126 ulated lymphangiogenesis through a VEGF-C/-D/VEGFR-3-independent pathway as a VEGFR-3 antagonist sele

127 d not influence binding to either VEGFR-2 or VEGFR-3, indicating distinct determinants of receptor bi

128 Thus, the VEGFR-3-induced lymphatic endothelial cell tip cell form

129 2 phosphorylation, whereas downregulation of VEGFR-3 inhibited ERK1/2 phosphorylation in LECs.

130 of the wild-type but not the mutant form of VEGFR-3 inhibited H(2)O(2)-induced apoptosis.

131 However, the blockade of VEGFR-3 inhibited only LV (P=0.0002) without concurrent

132 acological blockade of lymphangiogenesis via VEGFR-3 inhibition results in increased corneal thicknes

133 These results demonstrate that Notch1 and VEGFR-3 interact genetically, that Notch directly induce

134 Our data demonstrate that the FAK-VEGFR-3 interaction can be targeted by small druglike mo

135 Thus, the FAK/VEGFR-3 interaction may have a potential use to develop

136 ition to its involvement with cell survival, VEGFR-3 is a primary factor in lymphatic angiogenesis.

137 VEGFR-3 is a transmembrane receptor tyrosine kinase that

138 ne and primary murine BM cells, we show that VEGFR-3 is expressed on megakaryocytic progenitor cells

139 We have also shown that VEGFR-3 is overexpressed in human breast tumors and canc

140 scular endothelial growth factor receptor-3 (VEGFR-3) is a primary modulator of lymphatic endothelial

141 We have studied the expression of VEGFR-3, its ligand VEGF-C and the co-receptor neuropili

142 trophils, and epithelial cells expressed the VEGFR-3 ligands VEGF-C or VEGF-D.

143 ndent on VEGF-A/VEGFR-2 signaling but not on VEGFR-3 ligands.

144 lymphangiogenesis, showing its dependence on VEGFR-3 ligands.

145 are not known, and the possible existence of VEGFR-3(+) lymphatic or vascular EC progenitors has not

146 l analysis using lymphatic-specific markers: VEGFR-3, lymphatic endothelial hyaluronan receptor-1, to

147 not co-express any lymphatic markers such as VEGFR-3, LYVE-1 or SLC.

148 Regulating the function of VEGFR-3 may therefore be a mechanism for modulating adap

149 mation at least, in part, through inhibiting VEGFR-3-mediated ERK signaling pathway.

150 VEGFR-3-mediated lymphangiogenesis thus appears to modul

151 Intriguingly, the VEGFR-3-mediated signaling was required for the lymphati

152 rap (sVEGFR-3) and antibody directed against VEGFR-3 (mF4-31C1) significantly reduced tumor lymphangi

153 lial cells (LECs), whereas downregulation of VEGFR-3 mimicked the effect of CPX, blocking the tube fo

154 VEGF-C phosphorylated VEGFR-2 but not VEGFR-3, myosin light chain-2, or VE-cadherin.

155 VEGFR-3 neutralization for 2 weeks before mating blocked

156 lymphatic imaging to determine the effect of VEGFR-3 neutralization on lymph transport from paws to d

157 erine blood or lymphatic vascular densities, VEGFR-3 neutralization reduced serum and ovarian estradi

158 Embryos from VEGFR-3-neutralized dams developed normally when transfe

159 Compared with IgG treatment, VEGFR-3 neutralizing antibody treatment significantly de

160 scular endothelial growth factor receptor 3 (VEGFR-3) neutralizing antibody, VEGFR-2 neutralizing ant

161 Through induction of VEGFR-3, Notch increased endothelial cell responsiveness

162 trate, for the first time, the expression of VEGFR-3 on corneal dendritic cells (DC) and its up-regul

163 Recent evidence also suggests expression of VEGFR-3 on some tumor-associated macrophages.

164 scular endothelial growth factor receptor 3 (VEGFR-3) on the surface of microvascular endothelial cel

165 atment with blocking antibody against either VEGFR-3 or beta(1) integrin inhibited cell migration ind

166 r FN was able to induce the migration of 293/VEGFR-3 or DMEC cells to a limited extent.

167 scular endothelial growth factor receptor-3 (VEGFR-3 or Flt4) that appeared to be required for cell m

168 The tyrosine phosphorylation of VEGFR-3 or isoforms of PKC was completely inhibited by t

169 troducing a mutation at the kinase domain of VEGFR-3 or treatment with blocking antibody against eith

170 By using VEGFR-3-transfected 293 cells (293/VEGFR-3) or primary dermal microvascular endothelial cel

171 We then coupled a 12-amino-acid VEGFR-3 peptide, AV3, to a TAT cellular penetration sequ

172 ndothelial growth factor receptor (VEGFR)-2, VEGFR-3, platelet-derived growth factor receptor beta, F

173 Vascular endothelial growth factor-3 (VEGFR-3) plays a critical role in embryonic cardiovascul

174 The proportion of neointestinal VEGFR-3-positive cells increased and ultimately, tubular

175 The 10.1.1 antibody recognizes VEGFR-2- and VEGFR-3-positive lymphatic sinuses and vessels within ly

176 Anti-VEGFR-3 prevented migration of CD4 T cells into lymphati

177 Blockade of VEGFR-3 promoted endoreplication consistently.

178 /suppressor of hairless/Lag1 (CSL) bound the VEGFR-3 promoter and transactivated VEGFR-3 specifically

179 1, and both NF-kappaB and Prox1 activate the VEGFR-3 promoter leading to increased receptor expressio

180 VEGF-C signaling through VEGFR-3 promotes lymphangiogenesis, which is a clinicall

181 ptor tyrosine kinases, VEGFR-1, VEGFR-2, and VEGFR-3, promoting angiogenic and lymphangiogenic signal

182 These studies suggest that VEGFR-3 protects against oxidative damage in endothelial

183 and D mediate lymphangiogenesis through the VEGFR-3 receptor on lymphatic endothelia.

184 F-C-mediated Erk1/2 activation and abrogated VEGFR-3 receptor-dependent binding of VEGF-C to the lymp

185 Both VEGFR-2 and VEGFR-3 receptors were shown to be expressed in human sa

186 structural homology and activate VEGFR-2 and VEGFR-3, receptors on endothelial cells that signal for

187 scular endothelial growth factor receptor 3 (VEGFR-3) regulates cardiovascular development and physio

188 gh signaling via VEGF receptor (VEGFR)-2 and VEGFR-3, respectively.

189 sessed after antibody blockade of VEGFR-2 or VEGFR-3 RESULTS: Although high-dose bFGF stimulation ind

190 the results here show that the expression of VEGFR-3(S) is up-regulated in >75% of HBxAg positive hep

191 In conclusion, HBxAg may short circuit VEGFR-3(S) signaling in liver cancer.

192 Blocking VEGFR-3(S) signaling may be effective in preventing tumo

193 VEGFR-3(S) siRNA partially blocked the ability of HBxAg

194 VEGFR-3(S) up-regulation correlates with the expression

195 factor receptor-3 short form splice variant (VEGFR-3(S)) expression in HBxAg positive compared to neg

196 sed tumor lymphangiogenesis, indicating that VEGFR-3 signaling affects the rate of tumor cell entry i

197 20 genes that encode proteins acting around VEGFR-3 signaling but also downstream of other tyrosine

198 Inhibition of VEGFR-3 signaling completely prevented the growth of lym

199 iogenesis and vascular permeability and that VEGFR-3 signaling does not compensate for VEGFR-2 blocka

200 cular homeostasis by fine-tuning VEGFR-2 and VEGFR-3 signaling in ECs, suggesting its relevance in th

201 Here, we provide evidence that activation of VEGFR-3 signaling in response to hydrogen peroxide (H(2)

202 es during the development of OAD, and VEGF-C/VEGFR-3 signaling modulated innate and adaptive immune r

203 endothelial growth factor receptor (VEGFR)-2/VEGFR-3 signaling of lung lymphatics in sustained inflam

204 VEGFR-3 signaling plays an important role in development

205 Blockade of either VEGFR-2 or VEGFR-3 signaling reduces both HA and LA; however, the p

206 Vascular endothelial growth factor C/VEGFR-3 signaling through PI3Kalpha regulates the activi

207 Blockade of VEGFR-3 signaling using a small-molecule inhibitor inhib

208 scular endothelial growth factor receptor-3 (VEGFR-3) signaling significantly suppresses corneal anti

209 Our results thus suggest VEGFR-3-signaling as a novel strategy to regulate T-cell

210 The effects of VEGF-C156S, a VEGFR-3-specific agonist, and VEGF-A were also studied.

211 rate that implantation of pellets containing VEGFR-3-specific ligands (VEGF-C156S and recombinant mur

212 The implantation of pellets containing VEGFR-3-specific ligands also leads to the recruitment o

213 eduction of HA is significantly greater with VEGFR-3-specific ligands than that by VEGF-A or VEGF-C.

214 Consequently, a VEGFR-3-specific neutralizing antibody markedly inhibite

215 Collectively, our data suggest that VEGFR-3-specific signaling can induce new blood vessels,

216 ound the VEGFR-3 promoter and transactivated VEGFR-3 specifically in endothelial cells.

217 stimulator of hemangiogenesis (HA), whereas VEGFR-3 stimulates lymphangiogenesis (LA).

218 argeting domain of FAK and was homologous to VEGFR-3, suggesting these two tyrosine kinases physicall

219 truncated isoform of this molecule, soluble VEGFR-3 (sVEGFR-3), which is critical for corneal alymph

220 wed by sequential up-regulation of Prox1 and VEGFR-3 that preceded lymphangiogenesis by 4 and 2 days,

221 CLEC14A KO resulted in a marked reduction in VEGFR-3 that was concomitant with increases in VEGFR-2 e

222 ependence of lymphangiectasia on VEGFR-2 and VEGFR-3, the condition was not reversed by blocking both

223 Anti-VEGFR-3 therapy had no significant impact on growth of m

224 t whilst in the mouse there is only a single Vegfr-3 transcript, in humans there are two transcripts

225 By using VEGFR-3-transfected 293 cells (293/VEGFR-3) or primary d

226 Our data show that anti-VEGFR-3 treatment ameliorates lethal aGVHD and identifie

227 phosphorylation of the major VEGF-C receptor VEGFR-3 upon VEGF-C stimulation.

228 to investigate whether combined blockade of VEGFR-3 (vascular endothelial growth factor receptor-3)

229 eno-associated viral vector-mediated soluble VEGFR-3 (VEGF-C/D Trap) completely blocked lymphangiogen

230 Tammela et al. in Nature show that VEGFR-3, via Notch regulation, is present on endothelial

231 This increased tyrosine phosphorylation of VEGFR-3 was diminished by pretreatment with a blocking a

232 en or FN-induced tyrosine phosphorylation of VEGFR-3 was inhibited by treatment with cytochalasin D,

233 e, a hereditary lymphoedema-linked mutant of VEGFR-3 was not phosphorylated by H(2)O(2) treatment.

234 Blockade of VEGFR-3 was sufficient to inhibit the development of lym

235 In vivo, VEGFR-3 was upregulated in endothelial cells with active

236 mation of coronary arteries, whereas soluble VEGFR-3 was without effect.

237 A, exhibited enhanced potency for activating VEGFR-3, was able to promote increased COX-2 mRNA levels

238 al antibodies to the extracellular domain of VEGFR-3, we show that 11% +/- 1% of CD34(+) cells isolat

239 c growth in adult mice, but both VEGFR-2 and VEGFR-3 were required for the development of lymphangiec

240 cated by staining with laminin, VEGFR-2, and VEGFR-3, whereas Ad-VEGF-A(165) stimulated the selective

241 scular endothelial growth factor receptor 3 (VEGFR-3), with its cognate ligand vascular endothelial g