ライフサイエンスコーパス: Fc epsilon RI

1 Fc epsilon RI activation of mast cells is thought to inv

2 Fc epsilon RI aggregation induced the tyrosine phosphory

3 Fc epsilon RI aggregation induced tyrosine phosphorylati

4 Fc epsilon RI cross-linkage in mast cells results in rel

5 Fc epsilon RI cross-linking stimulates the release of al

6 Fc epsilon RI gamma (gamma) is a member of a group of re

7 Fc epsilon RI is composed of one alpha, one beta, and tw

8 Fc epsilon RI, Fc gamma RII, and Fc gamma RIII expressio

9 Fc epsilon RI- and SCF-mediated NTAL phosphorylation app

10 Fc epsilon RI-IgE interaction is highly species specific

11 Fc epsilon RI-induced tyrosine phosphorylation of total

12 Fc epsilon RI-mediated inositol phosphate production is

13 g factor receptor, Ig Fc epsilon receptor 1 (Fc epsilon RI), and tryptase.

14 lin E (IgE) receptor, Fc epsilon receptor 1 (Fc epsilon RI), have key roles in allergic diseases.

15 ma Fc epsilon fusion protein to co-aggregate Fc epsilon RI with a receptor containing an immunorecept

16 It amplifies Fc epsilon RI surface expression and signaling, resultin

17 ponse to mIgE binding is a result of such an Fc epsilon RI-IgE induced aggregation.

18 urse for cross-linking by multivalent Ag and Fc epsilon RI-mediated signaling, and they provide the m

19 Stem cell factor, TGF-beta, and Fc epsilon RI aggregation enhanced Fas expression.

20 The large surface area of IgE and Fc epsilon RI alpha that is implicated in complex format

21 motif, has therapeutic potential in IgE- and Fc epsilon RI-mediated diseases.

22 Unlike 1:1 FcgammaRIII:IgG and Fc epsilon RI:IgE complexes, two FcalphaRI molecules bin

23 all expressed high surface levels of Kit and Fc epsilon RI, each of which were functional, indicating

24 MCs resulted in a reduction of both Kit- and Fc epsilon RI-mediated degranulation.

25 g Ig Fc gamma RIII or both Fc gamma RIII and Fc epsilon RI.

26 ity of IgE to enhance mast cell survival and Fc epsilon RI expression may contribute to amplified all

27 the tyrosine kinases activated after TCR and Fc epsilon RI engagement.

28 ith anti-c-kit mAb), anti-IgE treatment, and Fc epsilon RI-deficient mice indicated a critical effect

29 ized, our results suggest that the zeta- and Fc epsilon RI gamma-chains are functional subunits of th

30 ed tyrosine phosphorylation of the zeta- and Fc epsilon RI gamma-chains, indicating their functional

31 ecific Ab coimmunoprecipitated the zeta- and Fc epsilon RI gamma-chains.

32 the signaling of antigen receptors, such as Fc epsilon RI, recruit tyrosine and inositol phosphatase

33 in -/- mast cells, including decreased basal Fc epsilon RI expression, slowed Fc epsilon RI internali

34 E can be a major regulator of mouse basophil Fc epsilon RI expression in vivo identifies a potentiall

35 ic (approximately 81%) reduction of basophil Fc epsilon RI expression compared with the corresponding

36 co-aggregation with Fc epsilon RI can block Fc epsilon RI-mediated reactivity.

37 ine, designated B6A4C1, is deficient in both Fc epsilon RI-mediated degranulation and biosynthesis of

38 , an inhibitor of PI3-kinase, inhibited both Fc epsilon RI- and SCFR-mediated JNK activation and part

39 protein is able to form complexes with both Fc epsilon RI and Fc gamma RII, and inhibit mast-cell an

40 Fas-mediated apoptosis was not augmented by Fc epsilon RI aggregation, and stem cell factor and TGF-

41 nhance the phosphorylation of LAT induced by Fc epsilon RI aggregation.

42 y induced in murine mast cells stimulated by Fc epsilon RI cross-linking, which is a major physiologi

43 In primary cultures of human mast cells, Fc epsilon RI aggregation induced a rapid translocation

44 In these reconstituted cells, Fc epsilon RI aggregation induced tyrosine phosphorylati

45 ty receptor for immunoglobulin E (designated Fc epsilon RI) is the member of the antigen (Ag) recepto

46 affinity receptor for immunoglobulin (Ig) E (Fc epsilon RI) on mast cells and basophils plays a key r

47 high affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells results in rapid tyrosine p

48 igh-affinity receptors for immunoglobulin E (Fc epsilon RI) on the surface of mast cells results in d

49 high affinity receptor for immunoglobulin E (Fc epsilon RI) results in the coordinate activation of t

50 that Syk plays a critical role in the early Fc epsilon RI-mediated signaling events.

51 ils failed to detect transcripts that encode Fc-epsilon RI or Fc-epsilon RII.

52 -4 acted synergistically with IgE to enhance Fc epsilon RI expression in these umbilical cord blood-d

53 mulation of mast cells through CD28 enhanced Fc epsilon RI-induced TNF-alpha secretion in a dose-depe

54 GEF1-deficient (-/-) mast cells and examined Fc epsilon RI-dependent responses.

55 ighly cytokinergic (HC) IgEs cause extensive Fc epsilon RI aggregation, which leads to potent enhance

56 e and release interleukin-6 (IL-6) following Fc epsilon RI ligation.

57 Mast cell degranulation following Fc epsilon RI aggregation is generally believed to be de

58 s, but not the SH2 domain, were critical for Fc epsilon RI-mediated degranulation and IL-6 secretion,

59 lls (LAT) is an adaptor protein critical for Fc epsilon RI-mediated mast cell activation.

60 tivation of Cdc42 and/or Rac is critical for Fc epsilon RI-mediated signaling that leads to Ca(2+) mo

61 ility and two proline residues important for Fc epsilon RI binding.

62 ctional, indicating IgE was not required for Fc epsilon RI expression on mast cells.

63 of eosinophil lysates using mAb specific for Fc epsilon RI alpha showed a distinct band of approximat

64 y of proinflammatory mediators secreted from Fc epsilon RI-activated mast cells, as well as sensitiza

65 ggregated with an activating receptor (e.g., Fc epsilon RI, B cell Ag receptor), Fc gamma RIIB is rap

66 Fc gamma Fc epsilon bound to both human Fc epsilon RI and Fc gamma RII.

67 phylaxis in transgenic mice expressing human Fc epsilon RI alpha.

68 The results demonstrate that the human Fc epsilon RI alpha chain alone not only confers the spe

69 The human Fc epsilon RI alpha chain gene with a 1.3-kb promoter re

70 Cell surface expression of the human Fc epsilon RI alpha chain was indicated by the specific

71 ctions, transgenic mice expressing the human Fc epsilon RI alpha chain were generated.

72 re with responses mediated through the human Fc epsilon RI receptor.

73 The transgenic human Fc epsilon RI alpha chain was complexed with the mouse b

74 regation of high affinity receptors for IgE (Fc epsilon RI) by soluble cross-linking ligands.

75 The high affinity receptor for IgE (Fc epsilon RI) has a central role in mast cell degranula

76 Aggregation of high affinity FcR for IgE (Fc epsilon RI) on mast cells activates intracellular sig

77 nking of the high affinity receptor for IgE (Fc epsilon RI), in the plasma membrane of mast cells, is

78 gE)-occupied high affinity receptor for IgE (Fc epsilon RI).

79 chain of the high affinity receptor for IgE (Fc epsilon RI-beta, MS4A2) are consistently associated w

80 tion of the high affinity receptors for IgE, Fc epsilon RI, on a rat mast cell line, RBL-2H3, stimula

81 conflicting data by measuring levels of IgE, Fc epsilon RI, and Fc epsilon RII in or on human eosinop

82 ramethyl-indocarbocyanine (diI-C18)) and IgE-Fc epsilon RI cross-linking in adherent RBL mast cells s

83 oss the C epsilon 3 domain may influence IgE-Fc epsilon RI interactions.

84 t structural constraints on cross-linked IgE-Fc epsilon RI complexes imposed by these rigid DNP-dsDNA

85 ay affect the functional consequences of IgE-Fc epsilon RI aggregation on the cell surface.

86 E, identified changes in the kinetics of IgE-Fc epsilon RI interaction.

87 Cross-linking of IgE-Fc epsilon RI on these cells stimulates robust tyrosine

88 e direct evidence for the association of IgE-Fc epsilon RI with specialized cholesterol-rich domains

89 e features of immunoglobulin E-receptor (IgE-Fc epsilon RI) aggregation that are critical for cellula

90 Ag-induced cross-linking of cell surface IgE-Fc epsilon RI receptor complexes.

91 eptionally slow dissociation rate of the IgE-Fc epsilon RI complex and, thus, of the ability of IgE t

92 e and the A-B loop in C epsilon 3 in the IgE-Fc epsilon RI interaction.

93 s, as well as an integrin and unliganded IgE-Fc epsilon RI.

94 To examine the role of c-Cbl and Cbl-b in Fc epsilon RI signaling, mast cell cultures from wild-ty

95 of PI 3-kinase, also revealed no defects in Fc epsilon RI-mediated PLC gamma 1 activation.

96 ysiological setting and of a role for Fgr in Fc epsilon RI-mediated signaling.

97 creased CpG concentration were identified in Fc epsilon RI-beta.

98 rs in parallel with IgE-induced increases in Fc epsilon RI surface expression but requires the contin

99 Cbl-b inactivation resulted in increases in Fc epsilon RI-induced Ca(2+) response and histamine rele

100 e the role of these four tyrosines of LAT in Fc epsilon RI-mediated mast cell activation, bone marrow

101 ine the role of SLP-76 domains and motifs in Fc epsilon RI signaling, SLP-76(-/-) BMMC were retrovira

102 on and its 'downstream' effector pathways in Fc epsilon RI-dependent mast cell activation.

103 A polymorphism in Fc epsilon RI-beta shows parent-of-origin effects when a

104 he adapter SLP-76 plays an essential role in Fc epsilon RI signaling, since SLP-76(-/-) bone marrow-d

105 rosine kinase Syk plays an essential role in Fc epsilon RI-mediated histamine release in mast cells b

106 y demonstrating an essential role for Syk in Fc epsilon RI signalling.

107 two tyrosines, Tyr342 and Tyr346 of Syk, in Fc epsilon RI-mediated signaling.

108 tion, suggesting a critical role for Y145 in Fc epsilon RI-mediated exocytosis.

109 ross an 18.1 Kb genomic region that includes Fc epsilon RI-beta.

110 how that antibodies recognizing CD81 inhibit Fc epsilon RI-mediated mast cell degranulation but, surp

111 k) to Fc epsilon RI is sufficient to inhibit Fc epsilon RI-induced calcium mobilization and extracell

112 Cyclosporin A inhibited Fc epsilon RI-mediated JNK and p38 activation, but did n

113 Wortmannin and cyclosporin A inhibited Fc epsilon RI-mediated production of TNF-alpha and IL-4

114 iated JNK activation and partially inhibited Fc epsilon RI, but not SCFR-mediated p38 activation.

115 Since we were able to detect intracellular Fc epsilon RI alpha, we examined its release from eosino

116 ed mathematical model of reactions involving Fc epsilon RI, Lyn, Syk, and a bivalent ligand that aggr

117 d in the sensitized and OVA-challenged mice; Fc epsilon RI-deficient mice showed comparable numbers o

118 to generate a mouse line in which the murine Fc epsilon RI alpha-chain has been replaced with its hum

119 owed the presence of FcR gamma-chain, but no Fc epsilon RI beta.

120 A coding variant of Gly237Glu in exon 7 of Fc epsilon RI beta gene showed association with atopic a

121 This activation of Fc epsilon RI initiates various tyrosine kinase-dependen

122 se Syk-deficient TB1A2 cells, aggregation of Fc epsilon RI induced no histamine release and no detect

123 Aggregation of Fc epsilon RI on mast cells and basophils leads to autop

124 Aggregation of Fc epsilon RI or Fc gamma RI led to an induction or accu

125 st cell activation induced by aggregation of Fc epsilon RI receptors with immunoglobulin E and antige

126 rogress in understanding specific aspects of Fc epsilon RI biology and biochemistry.

127 ect the intracellular signalling capacity of Fc epsilon RI.

128 ember of the zeta family, the gamma-chain of Fc epsilon RI (Fc epsilon RI gamma) within the TCR compl

129 oglobulin-like domains in the alpha-chain of Fc epsilon RI.

130 Here we show that antigen clustering of Fc epsilon RI on the rat mast-cell line (RBL-2H3) activa

131 on that the PLC gamma-dependent component of Fc epsilon RI-mediated calcium flux leading to degranula

132 nding of the soluble extracellular domain of Fc epsilon RI to IgE.

133 found that: 1) IgE-dependent enhancement of Fc epsilon RI expression was associated with a significa

134 chanism by which Kit mediates enhancement of Fc epsilon RI-mediated degranulation, cytoskeletal rearr

135 High level expression of Fc epsilon RI gamma chain replaces the deficient TCR zet

136 re strikingly enhanced surface expression of Fc epsilon RI than did IL-4 (at 0.1-100 ng/ml); similar

137 growth rates and cell surface expression of Fc epsilon RI were similar in the different cell populat

138 all required for cell surface expression of Fc epsilon RI, but only the alpha chain is involved in t

139 biological relevance of this soluble form of Fc epsilon RI alpha remains to be determined.

140 as a mediator of Fc gamma RIIB inhibition of Fc epsilon RI signal transduction in mast cells.

141 y 50%) concentration-dependent inhibition of Fc epsilon RI-mediated degranulation in human mast cells

142 n of molecules to inhibit the interaction of Fc epsilon RI alpha with its natural ligand and thus to

143 We now find that the level of Fc epsilon RI expression on bone marrow basophils in mic

144 rmore, our data strongly supports a model of Fc epsilon RI engagement leading to the sequential activ

145 We observed that overexpression of Fc epsilon RI gamma is associated with increased phospho

146 ase inhibitor had no effect on parameters of Fc epsilon RI-mediated PLC gamma activation, and had lit

147 ce that the PLC gamma 1-dependent pathway of Fc epsilon RI-mediated activation of mast cells is indep

148 -kinase may contribute to the later phase of Fc epsilon RI-mediated degranulation in human mast cells

149 y, all stimulate tyrosine phosphorylation of Fc epsilon RI beta, Syk, and linker for activation of T

150 Lyn-induced phosphorylation of Fc epsilon RI occurs in a cholesterol-dependent manner,

151 cs of stimulated tyrosine phosphorylation of Fc epsilon RI, the first identifiable biochemical step o

152 P-BSA-stimulated tyrosine phosphorylation of Fc epsilon RI.

153 hils possess a sizable intracellular pool of Fc epsilon RI alpha that is available for release, with

154 Thus, RabGEF1 is a negative regulator of Fc epsilon RI-dependent mast cell activation, and a lack

155 c-Cbl, functions as a negative regulator of Fc epsilon RI-induced degranulation.

156 Western blotting demonstrated the release of Fc epsilon RI alpha into the supernatant of cultured eos

157 wly recognized addition to the repertoire of Fc epsilon RI-mediated signaling systems is the activati

158 Stimulation of Fc epsilon RI results in the rapid association and activ

159 e cytoplasmic domain of the gamma subunit of Fc epsilon RI (CD8-gamma)) to examine the regulation of

160 gh the coding regions of the beta subunit of Fc epsilon RI (Fc epsilon RI-beta) has identified a nove

161 c segments of the beta and gamma subunits of Fc epsilon RI by the Src tyrosine kinase Lyn, which is a

162 fs (ITAMs) on the beta and gamma subunits of Fc epsilon RI, and Syk itself in the activation of Syk.

163 tyrosine phosphorylation of the subunits of Fc epsilon RI, Lyn, or Syk or of the Ras-guanine nucleot

164 drophobicity change within the C-terminus of Fc epsilon RI-beta.

165 However, Leu181lle, another variant of Fc epsilon RI beta related to atopy in British and Austr

166 study was performed with coding variants of Fc epsilon RI beta in relation to atopic and non-atopic

167 These results suggest that variants of Fc epsilon RI beta may be an important genetic cause of

168 vestigated the effects of IgE versus IL-4 on Fc epsilon RI surface expression in differentiated human

169 , mutation of Tyr346 had much less effect on Fc epsilon RI-dependent mast cell degranulation.

170 c-Cbl deficiency had no detectable effect on Fc epsilon RI-induced histamine release or on the phosph

171 at Cbl-b and c-Cbl have divergent effects on Fc epsilon RI signal transduction and that Cbl-b, but no

172 ven in the absence of significant effects on Fc epsilon RI surface expression; 3) when used together

173 amma may have negative regulatory effects on Fc epsilon RI-induced mast cell signaling and functions.

174 is review provides background information on Fc epsilon RI function combined with more detailed summa

175 ltured human mast cells after Fc gamma RI or Fc epsilon RI aggregation.

176 We found that the overexpressed Fc epsilon RI gamma chain colocalizes with the CD3 epsil

177 ding of Syk than ZAP70 to the phosphorylated Fc epsilon RI gamma-ITAM.

178 luble fragment of the high-affinity receptor Fc epsilon RI alpha-chain (sFc epsilon RI alpha).

179 accompany binding to the mast cell receptor Fc epsilon RI.

180 beta-chain of the high affinity IgE receptor Fc epsilon RI, I181L-V183L and E237G, have been found as

181 ed with the human high-affinity IgE receptor Fc epsilon RI, we demonstrate that ligands IGEL1.2 and D

182 arily through the high-affinity IgE receptor Fc epsilon RI.

183 lpha-chain of the high-affinity IgE receptor Fc-epsilon RI, but did detect transcripts that encode Ma

184 t aggregation of the high-affinity receptor (Fc epsilon RI) by allergen plays a pivotal role in type

185 mulation of mast cells via the IgE receptor (Fc epsilon RI) elicits production and release of numerou

186 ctivation of the high affinity IgE receptor (Fc epsilon RI) of mast cells, a member of the antigen re

187 s-linking of the high affinity IgE receptor (Fc epsilon RI) on mast cells induces a set of activation

188 t year to our understanding of IgE receptor (Fc epsilon RI) signaling in mast cells include studies w

189 gens through the high affinity IgE receptor (Fc epsilon RI), play a prominent role in anaphylaxis in

190 biochemical event proximal to IgE receptor (Fc epsilon RI)-stimulated tyrosine phosphorylation that

191 monomeric IgE (mIgE) to its type 1 receptor, Fc epsilon RI, on mast cells induces important responses

192 c IgE binding to its high-affinity receptor, Fc epsilon RI.

193 timulated via the immunoglobulin E receptor, Fc epsilon RI.

194 ure of the human high affinity IgE receptor, Fc epsilon RI alpha, in six different crystal forms, sho

195 tivation via the high-affinity IgE receptor, Fc epsilon RI, although many other functions have recent

196 ma RIIB with the high-affinity IgE receptor, Fc epsilon RI, leads to inhibition of Ag-induced degranu

197 mulation of mast cells via the IgE receptor, Fc epsilon RI, results in recruitment of the cytosolic t

198 ulin E complexed to high affinity receptors (Fc epsilon RI) on rat basophilic leukemia cells using bo

199 nding of IgE to high-affinity IgE receptors (Fc epsilon RI) on the surface of mast cells and basophil

200 tors, including high-affinity IgE receptors (Fc epsilon RI), is thought to be mediated by inositol-1,

201 r the transcription of Fc-epsilon receptors (Fc-epsilon RI, Fc-epsilon RII/CD23).

202 k with Y342F mutation failed to reconstitute Fc epsilon RI-initiated histamine release.

203 ZAP70 expression did not restore Fc epsilon RI signaling unless CD45 was coexpressed in t

204 ta family, the gamma-chain of Fc epsilon RI (Fc epsilon RI gamma) within the TCR complex.

205 egions of the beta subunit of Fc epsilon RI (Fc epsilon RI-beta) has identified a novel coding polymo

206 ction is highly species specific, and rodent Fc epsilon RI does not bind human IgE.

207 eased basal Fc epsilon RI expression, slowed Fc epsilon RI internalization, elevated IgE + Ag-induced

208 ining basal levels of Rabaptin-5 and surface Fc epsilon RI.

209 he exceptionally high number of cell surface Fc epsilon RI-bound monoclonal IgE yields, in the two-di

210 precipitation again failed to detect surface Fc epsilon RI alpha, although surface FcR gamma was easi

211 d induces a distinctly different signal than Fc epsilon RI cross-linking.

212 We report here that Fc epsilon RI also uses a Fyn kinase-dependent pathway t

213 mmunoprecipitation with anti-CD3 showed that Fc epsilon RI gamma-chains were associated with the TCR

214 The Fc epsilon RI-induced phosphorylation of Cbl was downstr

215 Although the Fc epsilon RI gamma-expressing T cells proliferated in r

216 Although the Fc epsilon RI-induced tyrosine phosphorylation of total

217 This was because zeta was replaced by the Fc epsilon RI gamma (FcR gamma).

218 a eukaryotic expression vector encoding the Fc epsilon RI gamma gene.

219 To examine the role of Syk in the Fc epsilon RI signaling pathway, we identified a variant

220 Y317F mutant resulted in an increase in the Fc epsilon RI-mediated tyrosine phosphorylation of phosp

221 c leukemia 2H3 cell line cells inhibited the Fc epsilon RI-induced tyrosine phosphorylation of the su

222 by enhanced tyrosine phosphorylation of the Fc epsilon RI beta and gamma chains and other cellular p

223 bined with the high expression levels of the Fc epsilon RI by mast cells.

224 ansiently transfected with components of the Fc epsilon RI complex (Lyn, Syk, and a chimeric CD8 rece

225 s results in tyrosine phosphorylation of the Fc epsilon RI gamma subunit and association of Syk with

226 To study the role of the Fc epsilon RI gamma-chain in TCR-gamma delta cells, a TC

227 phosphorylation, but upstream of most of the Fc epsilon RI-mediated protein tyrosine phosphorylations

228 This inhibition substantially suppresses the Fc epsilon RI-mediated calcium signal, but leaves intact

229 Taken together, our data suggest that the Fc epsilon RI gamma-chain associates with the TCR-gamma

230 Unlike the Fc epsilon RI response, SCF induced NTAL phosphorylation

231 nd secrete cytokines when stimulated through Fc epsilon RI, conclusively demonstrating an essential r

232 Thus Fc epsilon RI principally utilizes a SK pathway to mobil

233 Thus, Fc epsilon RI-dependent mast cell degranulation involves

234 Thus, Fc epsilon RI-mediated mast cell functional activation i

235 IgE binding to Fc epsilon RI was compared with surface plasmon resonanc

236 nly used to cross-link anti-DNP IgE bound to Fc epsilon RI to stimulate cellular responses, although

237 this hypothesis, recruitment of p62(dok) to Fc epsilon RI is sufficient to inhibit Fc epsilon RI-ind

238 raditional view, binding of monomeric IgE to Fc epsilon RI results in a number of biological outcomes

239 Thus, binding of HC IgEs to Fc epsilon RI induces adhesion of mast cells to fibronec

240 lipid mediators and cytokines in response to Fc epsilon RI aggregation.

241 Expression of the transgenic Fc epsilon RI on bone marrow-derived mast cells was 4.7

242 Cross-linking of the transgenic Fc epsilon RI with human IgE and antigens led to mast ce

243 of IgE in vivo can significantly upregulate Fc epsilon RI expression on mouse basophils, and genetic

244 ced after activation of human mast cells via Fc epsilon RI.

245 istinguishable from responses stimulated via Fc epsilon RI.

246 concert with immunoreceptor stimulation via Fc epsilon RI.

247 The in vivo Fc epsilon RI-induced tyrosine phosphorylation of wild-t

248 signaling complexes that are assembled when Fc epsilon RI and other Ag receptors are engaged, new in

249 hibitory motif and whose co-aggregation with Fc epsilon RI can block Fc epsilon RI-mediated reactivit

250 ligation of Fc gamma RIIb1 with BCR and with Fc epsilon RI on mast cells leads to recruitment of the

251 in vitro kinase activity and associated with Fc epsilon RI gamma after receptor aggregation, it was n

252 jor initial signaling events associated with Fc epsilon RI-mediated activation of human mast cells (H

253 strate that Fc gamma RIIB coaggregation with Fc epsilon RI stimulates enhanced SHIP tyrosine phosphor

254 via aggregation of Fc gamma RI compared with Fc epsilon RI.