ライフサイエンスコーパス: JAM-A

1 JAM-A also is expressed on the surface of circulating he

2 JAM-A and AF-6 were expressed at relatively high levels

3 JAM-A dimerization on a common cell surface (in cis) has

4 JAM-A is reported to contain N-glycans, but the extent o

5 JAM-A is required for establishment of viremia and viral

6 JAM-A is robustly expressed in normal human mammary epit

7 JAM-A localizes to tight junctions and contributes to pa

8 JAM-A mutants incapable of dimer formation form complexe

9 JAM-A or CD9 knockdown impairs endothelial cell migratio

10 JAM-A recruits Csk to the integrin-c-Src complex, where

11 JAM-A redistribution was associated with internalization

12 JAM-A serves many roles and contributes to barrier funct

13 JAM-A-deficient mice and cultured epithelial cells demon

14 JAM-A-deficient platelets showed increased aggregation a

15 The F11-receptor (F11R) (a.k.a. JAM-1, JAM-A, CD321) is a cell adhesion molecule of the immunog

16 Expression of a JAM-A mutant lacking a cytoplasmic tail in nonpermissive

17 ohydrate and junctional adhesion molecule A (JAM-A) and internalization by beta1 integrin.

18 (T3D/55) use junctional adhesion molecule A (JAM-A) as a receptor.

19 glycans and junctional adhesion molecule A (JAM-A) as attachment receptors.

20 Junctional adhesion molecule A (JAM-A) is a broadly expressed adhesion molecule that reg

21 Junctional adhesion molecule A (JAM-A) is a unique tight junction (TJ) transmembrane pro

22 , CLDN4, and junctional adhesion molecule A (JAM-A) subunits is induced at the GL.

23 PDZ3 ligand, junctional adhesion molecule A (JAM-A) to determine how the activity of different domain

24 irus engages junctional adhesion molecule A (JAM-A) to disseminate hematogenously.

25 recruited by junctional adhesion molecule A (JAM-A) to primordial junctions where aPKC is activated b

26 Junctional adhesion molecule A (JAM-A), a member of the cortical thymocyte marker of the

27 we show that junctional adhesion molecule A (JAM-A), a tight junction protein, is a key negative regu

28 proteins is junctional adhesion molecule A (JAM-A), an Ig fold transmembrane protein.

29 ace glycans, junctional adhesion molecule A (JAM-A), and the Nogo-1 receptor (depending on the cell t

30 1), CD99 and junctional adhesion molecule A (JAM-A), but apparently not vascular endothelial cell-spe

31 ttachment to junctional adhesion molecule A (JAM-A), virions undergo clathrin-mediated endocytosis fo

32 ous receptor junctional adhesion molecule A (JAM-A).

33 ohydrate and junctional adhesion molecule A (JAM-A).

34 ohydrate and junctional adhesion molecule A (JAM-A).

35 Mice lacking junctional adhesion molecule A (JAM-A, encoded by F11r) exhibit enhanced intestinal epit

36 ind to human Junctional Adhesion Molecule-A (JAM-A) and alpha4 integrin, respectively.

37 glycans and junctional adhesion molecule-A (JAM-A) and enters cells by receptor-mediated endocytosis

38 eceptors and junctional adhesion molecule-A (JAM-A) and is thought to undergo a conformational change

39 s: occludin, junctional adhesion molecule-A (JAM-A) and N-cadherin at the BTB.

40 bind to both junctional adhesion molecule-A (JAM-A) and sialic acid are the most potent inducers of a

41 e identify the junction adhesion molecule-A (JAM-A) as a key target for miR-34/449 in the developing

42 tion protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell

43 Junctional adhesion molecule-A (JAM-A) is a member of the immunoglobulin family with div

44 Junctional adhesion molecule-A (JAM-A) is a serotype-independent receptor for reovirus.

45 Junctional adhesion molecule-A (JAM-A) is a tight junction protein that serves as a rece

46 Junctional adhesion molecule-A (JAM-A) is a tight junction-associated adhesion protein p

47 Junctional adhesion molecule-A (JAM-A) is a tight junction-associated signaling protein

48 Junctional adhesion molecule-A (JAM-A) is a TJ-associated protein that regulates barrier

49 Junctional adhesion molecule-A (JAM-A) is a transmembrane component of tight junctions t

50 Junctional adhesion molecule-A (JAM-A) is a transmembrane tight junction protein that ha

51 Junctional adhesion molecule-A (JAM-A) is an adherens and tight junction protein express

52 y shown that junctional adhesion molecule-A (JAM-A) renders protection from thrombosis by suppressing

53 Junctional adhesion molecule-A (JAM-A) serves as a serotype-independent receptor for mam

54 of this study provide new information about JAM-A expression in tight junctions of the human corneal

55 Although we understand much about JAM-A, little is known regarding the protein's role in m

56 permeability similar to that observed after JAM-A loss.

57 s, we generated strains of mice with altered JAM-A expression in these cell types and assessed bloods

58 Endothelial ICAM-1 and JAM-A both colocalized with the ringlike LFA-1 cluster.

59 engagement of cell-surface carbohydrate and JAM-A by the length and IDR mutant viruses.

60 junction proteins such as ZO-1, claudin, and JAM-A; however, exposure of SCs to inflammatory mediator

61 eased in the trJAM-A(-/-) apoe(-/-)mice, and JAM-A-deficient platelets showed increased binding to mo

62 to the cell surface, reovirus particles and JAM-A codistribute into each of these compartments.

63 or hydrogen-bond interactions with apposing JAM-A monomers abolishes the capacity of JAM-A to form d

64 To assess JAM-A function in the lung, we depleted JAM-A in primary

65 We also show that integrin-associated JAM-A is tyrosine phosphorylated and is rapidly dephosph

66 A functional link between JAM-A and beta1 integrin was confirmed by restoration of

67 cell lines, an inverse relationship between JAM-A expression and the ability of these cells to migra

68 In addition, native MS analysis of bsAb/JAM-A immune complexes revealed that bsAb can bind up to

69 ued by inhibition of ROCK and phenocopied by JAM-A, JACOP, or p114RhoGEF down-regulation.

70 egrin, which responds to bFGF stimulation by JAM-A release to regulate mitogen-activated protein kina

71 In endothelial cells, JAM-A has been implicated in basic fibroblast growth fac

72 In contrast, JAM-A deficiency in bone marrow cells impeded monocyte d

73 Overexpression of dimerization-defective JAM-A mutants in 293T cells inhibited cell spreading and

74 rt the effects of cis-dimerization-defective JAM-A mutants on epithelial cell migration and adhesion.

75 ed the intestinal mucosa of JAM-A-deficient (JAM-A(-/-)) mice for evidence of enhanced permeability a

76 Protein phosphatase 2A dephosphorylates JAM-A at S285, suggesting that it antagonizes the activi

77 sess JAM-A function in the lung, we depleted JAM-A in primary alveolar epithelial cells using shRNA.

78 he Hz6F4 family preferentially binds dimeric JAM-A.

79 cycling to the membrane surface occur during JAM-A redistribution.

80 e dimer interface are required for efficient JAM-A engagement of strain type 3 Dearing sigma1.

81 a1 integrin cDNA, along with a cDNA encoding JAM-A, in nonpermissive chicken embryo fibroblasts confe

82 Our data identify endothelial JAM-A as an important effector molecule integrating athe

83 ion of LFA-1 and ICAM-1, but not endothelial JAM-A.

84 nt and luminal redistribution of endothelial JAM-A and were preferentially protected by its deficienc

85 expression and redistribution of endothelial JAM-A was increased by oxidized low-density lipoprotein,

86 We found that endothelial JAM-A but not hematopoietic JAM-A facilitates reovirus T

87 Thus, endothelial JAM-A does not appear to contribute to adhesion or trans

88 M-A reveals that both sigma1 proteins engage JAM-A with similar affinities and via conserved binding

89 These results indicate that reovirus engages JAM-A monomers via residues found mainly on beta-strands

90 ngs identify N-glycosylation as critical for JAM-A's many functions.

91 tetraspanin CD9 as novel binding partner for JAM-A in endothelial cells.

92 w that glycosylation of N185 is required for JAM-A-mediated reduction of cell migration.

93 Antibodies specific for JAM-A were capable of inhibiting infections of HeLa cell

94 Colonic mucosa from JAM-A(-/-) mice had normal epithelial architecture but i

95 Cell adhesion genes, JAM-A and FSCN1, were downregulated with overexpression

96 ntributions of endothelial and hematopoietic JAM-A to reovirus dissemination and pathogenesis, we gen

97 that endothelial JAM-A but not hematopoietic JAM-A facilitates reovirus T1L bloodstream entry and egr

98 However, JAM-A is dispensable for reovirus replication in the CNS

99 We show that human JAM-A contains a single N-glycan at N185 and that this r

100 We show that impaired JAM-A expression in endothelial cells reduced mononuclea

101 the colonic mucosa of JAM-A(-/-) mice and in JAM-A small interfering RNA-treated epithelial cells.

102 omatic or endothelium-specific deficiency in JAM-A and bone marrow chimeras with JAM-A-deficient leuk

103 ls after overexpression of beta1 integrin in JAM-A dimerization-defective cells.

104 icated involvement of RhoA and Rho kinase in JAM-A relocalization.

105 sed transepithelial electrical resistance in JAM-A(-/-) mice.

106 hemokine (C-C motif) ligand 2 (CCL2) induced JAM-A redistribution from the interendothelial cell area

107 By ~20 min, most internalized JAM-A moved to the brain endothelial cell apical membran

108 To corroborate these findings, we introduced JAM-A or the structurally related JAM family members JAM

109 In the present study, they investigate JAM-A expression in the human corneal endothelium and re

110 To investigate JAM-A function in ARPE-19 cells, ARPE-19 monolayers were

111 Junctional adhesion molecule 1 (JAM1/JAM-A/F11R) is a tight junction-associated transmembrane

112 es and expressed mutant forms of full-length JAM-A in Chinese hamster ovary cells to assess reovirus

113 On alphaIIbbeta3 ligation, JAM-A was shown to be dephosphorylated, which could be p

114 gulates barrier; however, mechanisms linking JAM-A to epithelial permeability are poorly understood.

115 rowth factor (VEGF), respectively, CD9 links JAM-A specifically to alphavbeta3 integrin.

116 n (TJ) include Junctional Adhesion Molecule (JAM-A), which has been implicated in the regulation of b

117 ngs indicate that CD9 incorporates monomeric JAM-A into a complex with alphavbeta3 integrin, which re

118 CD9 interacts predominantly with monomeric JAM-A, which suggests that bFGF induces signaling by tri

119 ous tubules, the approximately 32 kDa murine JAM-A is present in elongated spermatids and in the plas

120 We purified mutant JAM-A ectodomains for solution-phase and surface plasmon

121 anine substitutions to residues 43NNP45 (NNP-JAM-A) within the predicted trans-dimerization site did

122 revealed decreased association forces in NNP-JAM-A compared with WT and cis-null JAM-A.

123 Expression of nonphosphorylatable JAM-A/S285A interferes with single lumen specification d

124 n, antibodies against PECAM or CD99, but not JAM-A, block transcellular migration.

125 In contrast, beads coated with cis-null JAM-A demonstrated enhanced clustering similar to that o

126 d that expression of trans- but not cis-null JAM-A mutants decreased Rap2 activity.

127 s in NNP-JAM-A compared with WT and cis-null JAM-A.

128 is of tight junction (TJ) proteins occludin, JAM-A, and claudin-1.

129 ciated integral membrane proteins: occludin, JAM-A, and N-cadherin.

130 The ability of JAM-A to attenuate cell invasion correlated with the for

131 ovirus infection initiated in the absence of JAM-A and sialic acid results in apoptosis, Chinese hams

132 Absence of JAM-A results in impaired c-SrcY(529) phosphorylation an

133 In the absence of JAM-A, other tight junction proteins were mislocalized,

134 fection experiments revealed accumulation of JAM-A at sites between transfected cells, which was lost

135 ighly migratory, express the least amount of JAM-A.

136 ing JAM-A monomers abolishes the capacity of JAM-A to form dimers.

137 Deletion of JAM-A causes a gain-of-function in platelets, with lower

138 Detection of JAM-A in human sperm proteins indicates that its role ma

139 Dimerization of JAM-A is dependent on the sequence RVE in the amino-term

140 Trans-dimerization of JAM-A may thus act as a barrier-inducing molecular switc

141 e results suggest that trans-dimerization of JAM-A occurs at a unique site and with different affinit

142 These results suggest that dimerization of JAM-A regulates cell migration and adhesion through indi

143 alization and expression after disruption of JAM-A dimerization suggested that internalization of bet

144 rane-distal immunoglobulin-like D1 domain of JAM-A is required for homodimerization and binding to re

145 ssays were performed to assess the effect of JAM-A antibody on ARPE-19 monolayer permeability.

146 Assessment of effects of JAM-A dimerization on cell signaling revealed that expre

147 Notably, these proinflammatory effects of JAM-A-deficient platelets could be abolished by the inhi

148 he HIV-induced decrease in the expression of JAM-A and occludin was restored by inhibition of MMP act

149 Expression of JAM-A and the AF-6 isoforms actually decreased when tigh

150 oscopy was used to investigate expression of JAM-A and the related proteins JAM-C, CAR, and AF-6 in t

151 Expression of JAM-A in human corneal endothelium, human RPE tissue, an

152 -NT did not alter cell surface expression of JAM-A or attachment of reovirus to cells.

153 Expression of JAM-A was observed in human corneal endothelium, and its

154 In addition, expression of JAM-A was observed in human RPE and in intercellular jun

155 The expression of JAM-A was observed in the tight junctions of rabbit corn

156 effect was an increase in the expression of JAM-A, AF-6, and PAR-3 that correlated with a redistribu

157 th Afadin was dependent on the expression of JAM-A.

158 ion of sigma1 and requires the expression of JAM-A.

159 This study investigates the fate of JAM-A during inflammatory TJ complex remodeling and para

160 lity is consistent with previous findings of JAM-A function in epithelial tight junctions and suggest

161 o investigate the expression and function of JAM-A in the corneal endothelium.

162 To characterize cell-specific functions of JAM-A in atherosclerosis, we used apolipoprotein E-defic

163 N-glycosylation of JAM-A is required for the protein's ability to reinforce

164 Finally, we show that N-glycosylation of JAM-A regulates leukocyte adhesion and LFA-1 binding.

165 ccelerate the kinetics of internalization of JAM-A, N-cadherin, and occludin versus controls.

166 GF-beta3-induced increase in the kinetics of JAM-A and occludin endocytosis was abolished, making the

167 Furthermore, knockdown of JAM-A using short interfering RNAs enhanced the invasive

168 ratory MDA-MB-468 cells have lower levels of JAM-A on the cell surface.

169 AN nephrosis increased the protein levels of JAM-A, occludin, cingulin, and ZO-1 several-fold in glom

170 e least, are found to express high levels of JAM-A, whereas the more migratory MDA-MB-468 cells have

171 n E-cadherin in cells with reduced levels of JAM-A.

172 Localization of JAM-A was compared with the tight junction-associated pr

173 In cultured cells, loss of JAM-A caused an approximately 30% decrease in transepith

174 Furthermore, loss of JAM-A could be used as a biomarker for aggressive breast

175 stent with findings in other organs, loss of JAM-A decreased beta1 integrin expression and impaired f

176 Additionally, loss of JAM-A resulted in elevated mucosal and serum IgA that wa

177 Loss of JAM-A, Afadin, or PDZ-GEF2, but not ZO-1 or PDZ-GEF1, si

178 and variability, suggesting a likely mode of JAM-A binding via a conserved surface at the base of the

179 e epithelial specific, because monolayers of JAM-A(-/-) epithelial cells also demonstrated increased

180 claudin-10 and -15 in the colonic mucosa of JAM-A(-/-) mice and in JAM-A small interfering RNA-treat

181 Thus, we analyzed the intestinal mucosa of JAM-A-deficient (JAM-A(-/-)) mice for evidence of enhanc

182 Overexpression of JAM-A in MDA-MB-231 cells inhibited both migration and i

183 pression of AF-6, a known binding partner of JAM-A, was also observed in the tight junction in a patt

184 of the tight junction and binding partner of JAM-A.

185 The localization pattern of JAM-A in the RPE and ARPE-19 monolayers was similar to t

186 Finally, we show that phosphorylation of JAM-A at Ser-284 is required for RhoA activation in resp

187 vely at the TJs, and S285 phosphorylation of JAM-A is required for the development of a functional ep

188 Reduction of JAM-A resulted in a striking change in cell morphology,

189 rge molecules, revealing a potential role of JAM-A in controlling perijunctional actin cytoskeleton i

190 These findings demonstrate a complex role of JAM-A in intestinal homeostasis by regulating epithelial

191 These data demonstrate a direct role of JAM-A in mechanosignaling and control of RhoA and implic

192 These findings support a key role of JAM-A in promoting tight junction homeostasis and lung b

193 On injury, the enhanced susceptibility of JAM-A(-/-) mice to edema correlated with increased, tran

194 meability, we assessed the susceptibility of JAM-A(-/-) mice to the induction of colitis with dextran

195 the apical surface, and it was dependent on JAM-A.

196 We found that tension imposed on JAM-A activates RhoA, which leads to increased cell stif

197 n fully polarized cells, S285-phosphorylated JAM-A is localized exclusively at the TJs, and S285 phos

198 inase (Csk) binds to tyrosine phosphorylated JAM-A through its Src homology 2 domain.

199 trongly suggest that tyrosine-phosphorylated JAM-A is a Csk-binding protein and functions as an endog

200 to primordial junctions, aPKC phosphorylates JAM-A at S285 to promote the maturation of immature cell

201 Our data suggest that aPKC phosphorylates JAM-A at S285 to regulate cell-cell contact maturation,

202 l interfering RNA oligonucleotides prevented JAM-A relocalization, suggesting that macropinocytosis a

203 on of p38 MAPK and of the junctional protein JAM-A.

204 aphragms contain the tight junction proteins JAM-A (junctional adhesion molecule A), occludin, and ci

205 The proteins JAM-A, AF-6, PAR-3 and PAR-6 have been implicated in the

206 nt roles in testis where the closely-related JAM-A, JAM-B, and JAM-C are found.

207 ation of microRNA (miR)-145, which repressed JAM-A.

208 g residues alters the kinetics of the sigma1-JAM-A binding interaction.

209 Thus, sigma1-JAM-A interactions are unlikely to explain the differenc

210 Reovirus virions bind to soluble JAM-A and NgR1, while infectious disassembly intermediat

211 bility and lesion formation, whereas somatic JAM-A deletion revealed no significant effects.

212 Upon agonist stimulation, JAM-A is dephosphorylated on the tyrosine, allowing the

213 n in epithelial tight junctions and suggests JAM-A may have a role in the regulation of RPE barrier f

214 CD9 acts as scaffold and assembles a ternary JAM-A-CD9-alphavbeta3 integrin complex from which JAM-A

215 sting that cell surface molecules other than JAM-A mediate viral internalization following attachment

216 unctions of the corneal endothelium and that JAM-A has a major role in maintaining the corneal endoth

217 may be conserved in sperm motility and that JAM-A may be a candidate gene for the analysis of idiopa

218 We conclude that JAM-A normally limits platelet accumulation by inhibitin

219 We have previously demonstrated that JAM-A regulates cell migration by dimerization of the me

220 The results provide new evidence that JAM-A and its binding partner AF-6 are expressed in tigh

221 hemical and structural studies indicate that JAM-A forms cis-homodimers, the functional significance

222 Here we report that JAM-A associates directly with ZO-2 and indirectly with

223 Here, we report that JAM-A is physically and functionally associated with the

224 ection of lipopolysaccharide, we report that JAM-A(-/-) mice showed increased susceptibility to pulmo

225 The authors recently reported that JAM-A is expressed in rabbit corneal endothelium and tha

226 In this study, we show that JAM-A associates with integrin alphaIIbbeta3 in resting

227 Here we show that JAM-A in resting platelets functions as an endogenous in

228 The findings show that JAM-A is involved in sperm tail formation and is essenti

229 These findings suggest that JAM-A dimerization facilitates formation of a complex wi

230 Further experiments suggest that JAM-A does not regulate actin turnover but modulates act

231 These results suggest that JAM-A regulates epithelial permeability via association

232 Evidence suggests that JAM-A is important for the regulation of tight junction

233 e cell migration, and evidence suggests that JAM-A may form homodimers between cells (in trans).

234 Analyses of cells expressing the JAM-A dimerization-defective mutant proteins revealed di

235 e head domain via epitopes distinct from the JAM-A-binding site.

236 Mutation of residues in the JAM-A dimer interface that participate in salt-bridge or

237 structure-guided mutational analysis of the JAM-A dimer interface to identify determinants of reovir

238 Thus, JAM-A recruits Csk to the integrin-c-Src complex in rest

239 The observation that antibodies to JAM-A increase ARPE-19 monolayer permeability is consist

240 en used to test the effects of antibodies to JAM-A on corneal swelling.

241 ARPE-19 monolayers treated with antibody to JAM-A demonstrated a 33% increase in permeability to 10,

242 he effect of a function-blocking antibody to JAM-A on the permeability of cultured RPE cell monolayer

243 treated with a function-blocking antibody to JAM-A or an isotype-matched control.

244 bit corneal endothelium and that antibody to JAM-A produces corneal swelling.

245 performed in which a monoclonal antibody to JAM-A was shown to increase rabbit corneal swelling by 6

246 nfectious subvirion particles, which bind to JAM-A but bypass a requirement for proteolytic uncoating

247 d complexes, indicating that sigma1 binds to JAM-A monomers.

248 cture of serotype 3 reovirus sigma1 bound to JAM-A reveals that both sigma1 proteins engage JAM-A wit

249 sassembly intermediates (ISVPs) bind only to JAM-A.

250 g pathways activated by binding of sigma1 to JAM-A and sialic acid are dispensable for reovirus-media

251 Mice with or without platelet-specific (tr)JAM-A-deficiency in an apolipoprotein e (apoe(-/-)) back

252 Although DSS-treated JAM-A(-/-) animals had increased clinical disease compar

253 ts that bFGF induces signaling by triggering JAM-A dimerization.

254 ad that are indistinguishable from wild-type JAM-A-sigma1 head complexes, indicating that sigma1 bind

255 ting that strains of all three serotypes use JAM-A as a receptor.

256 We also demonstrate that T1L/T3DM2 utilizes JAM-A more efficiently than T1L.

257 elial cell area to the apical surface, where JAM-A played a role as a leukocyte adhesion molecule par

258 In this study, we investigated whether JAM-A also mediates the attachment of the prototype reov

259 -CD9-alphavbeta3 integrin complex from which JAM-A is released upon bFGF stimulation.

260 iency in JAM-A and bone marrow chimeras with JAM-A-deficient leukocytes.

261 Of importance, microspheres coated with JAM-A containing alanine substitutions to residues 43NNP

262 F2 colocalized and coimmunoprecipitated with JAM-A.

263 ent protein sigma1 alone and in complex with JAM-A.

264 attributable to differences in contacts with JAM-A.

265 we show that aPKC can interact directly with JAM-A in a PAR-3-independent manner.

266 3D/55 sigma1 protein interacts directly with JAM-A, but the determinants of receptor-binding specific

267 d that both antibodies likely interfere with JAM-A engagement by steric hindrance.

268 capable of infecting cells transfected with JAM-A but not those transfected with JAM-B or JAM-C.

269 similar to that observed with wild-type (WT) JAM-A.