ライフサイエンスコーパス: JAM-C

1 JAM-C expressed on both murine B16 melanoma cells as wel

2 JAM-C expression was identified in human and murine mela

3 JAM-C has been implicated in leukocyte transendothelial

4 JAM-C inhibition significantly decreased the chemokine-i

5 JAM-C is an adhesion molecule that is expressed on cells

6 JAM-C knockdown caused a delay in the hfRPE cell polariz

7 JAM-C localized at the tight junctions of cultured hfRPE

8 JAM-C localizes specifically in the tight junctions of h

9 JAM-C may therefore provide a novel molecular target for

10 JAM-C surface expression in HUVEC was uniformly low, and

11 JAM-C thereby mediated both leukocyte adhesion and leuko

12 JAM-C was also expressed in human sural nerves with an e

13 JAM-C was also expressed on the surface of OA ST and RA

14 JAM-C was essential for the regulation of endothelial ac

15 JAM-C was highly expressed by RA ST lining cells, and it

16 JAM-C(-/-) mice as well as endothelial-specific JAM-C-de

17 d in the HT-lo/diss variant, whereas NCAM-1, JAM-C, and TF levels were increased in the HT-hi/diss va

18 ndidates, four targets (i.e. TIMP-2, NCAM-1, JAM-C, and tissue factor (TF)) were selected for further

19 ing in vivo differences in levels of TIMP-2, JAM-C, and TF were demonstrated in primary tumors grown

20 We have identified DHHC7 as a JAM-C palmitoylating enzyme by screening all known palmi

21 ractility and VE-cadherin-mediated adhesion, JAM-C helps to regulate vascular permeability and pathol

22 the primordial cell-cell contacts and after JAM-C knockdown, the organization of N-cadherin and ZO-1

23 presence of neutralizing antibodies against JAM-C.

24 studies of the JAM family members JAM-A and JAM-C have expanded the roles of these proteins to inclu

25 increases are essential in angiogenesis, and JAM-C blockade reduced hyperpermeability and neovascular

26 turally related JAM family members JAM-B and JAM-C into Chinese hamster ovary cells, which are poorly

27 gnificant sub-functionalisation of JAM-B and JAM-C orthologues with respect to binding strength (but

28 the heterotypic adhesion molecules JAM-B and JAM-C.

29 where the closely-related JAM-A, JAM-B, and JAM-C are found.

30 ansepithelial migration, both JAM-C mAbs and JAM-C/Fc chimeras significantly inhibited the rate of PM

31 also formed a stable complex with Pals1 and JAM-C (a component of the apical ES) in normal testes.

32 Accordingly, anti-JAM-C antibodies blocked adhesion of JAM-C-expressing B

33 Neutralizing anti-JAM-C Abs inhibited RA synovial fluid-induced HMVEC chem

34 Long-term administration of anti-JAM-C antibodies prevented engraftment of JAM-Cpos lymph

35 Treatment with anti-JAM-C antibodies in short-term experiments reduced migra

36 followed by binding to desmosomal-associated JAM-C are key elements of the transmigration response.

37 o flow model showed that functional blocking JAM-C mAb alone had no inhibitory effect on polymorphonu

38 ssays of PMN transepithelial migration, both JAM-C mAbs and JAM-C/Fc chimeras significantly inhibited

39 xpression of junctional adhesion molecule C (JAM-C) at EC junctions, and they were enhanced by blocka

40 the role of junctional adhesion molecule C (JAM-C) in mediating leukocyte recruitment and retention

41 Junctional adhesion molecule C (JAM-C) is a transmembrane protein with significant roles

42 Junctional adhesion molecule C (JAM-C) is an immunoglobulin superfamily protein expresse

43 Junctional adhesion molecule C (JAM-C) is expressed by vascular endothelium and human bu

44 The junctional adhesion molecule C (JAM-C) was recently shown to undergo a heterophilic inte

45 s, including junctional adhesion molecule-C (JAM-C) and myelin-associated glycoprotein (MAG).

46 e identified junctional adhesion molecule-C (JAM-C) as a novel player in melanoma metastasis to the l

47 Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions be

48 Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed by endothelial

49 The junctional adhesion molecule-C (JAM-C) was recently shown to be a counter receptor for t

50 superfamily, junctional adhesion molecule-C (JAM-C), is critically required for the differentiation o

51 ty of the EC junctional adhesion molecule-C (JAM-C).

52 ng routes of junctional adhesion molecule-C (JAM-C).

53 n quiescent microvascular endothelial cells, JAM-C localized mainly intracellularly, and was recruite

54 Although under quiescent conditions, JAM-C predominantly localized to interendothelial cell-c

55 Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, mu

56 JAM-C-positive) and germinal center-derived (JAM-C-negative) B-cell lymphomas.

57 the classification of marginal zone-derived (JAM-C-positive) and germinal center-derived (JAM-C-negat

58 Dynamic JAM-C trafficking and degradation are necessary for junc

59 d vascular leakage, suggesting a role for EC JAM-C in the development of functional tumor vessels.

60 findings provide evidence for a role for EC JAM-C in tumor growth and aggressiveness as well as recr

61 However, tumor microvessels from EC JAM-C-deficient mice exhibited reduced pericyte coverage

62 , survival in this model was increased in EC JAM-C knockouts (KOs; 88 vs. 96 d, P=0.04) and reduced i

63 tumor growth was significantly reduced in EC JAM-C KOs (87% inhibition at 10 wk, P<0.0005), this was

64 (KOs; 88 vs. 96 d, P=0.04) and reduced in EC JAM-C transgenics (88 vs. 78.5 d, P=0.03), mice deficien

65 Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of

66 nt in promoting tumor growth, the role of EC JAM-C in tumor development was investigated using the ID

67 .03), mice deficient in or overexpressing EC JAM-C, respectively.

68 Thus, upon oxLDL stimulation endothelial JAM-C functions as both an adhesion, as well as a transm

69 , but not a DHHC7 catalytic mutant, enhances JAM-C S-palmitoylation.

70 h muscle cells (HASMC) were found to express JAM-C, and oxLDL, as well as enzymatically modified LDL

71 noma cell line NCI-H522 was found to express JAM-C.

72 othelial cells that constitutively expressed JAM-C in cell-cell contacts, in quiescent microvascular

73 Fibroblast JAM-C expression was also analyzed using Western blottin

74 Finally, JAM-C promotes the basal-to-apical transmigration of gra

75 ies identified JAM-B as the major ligand for JAM-C, whereas homotypic JAM-C interactions remained at

76 of transmigration of PMN or evoke a role for JAM-C in transendothelial migration.

77 During initial junction formation JAM-C was recruited to the primordial cell-cell contacts

78 iles and gene expression data generated from JAM-C-expressing leukemic cells, we defined a single cel

79 derlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defect

80 Sciatic nerves from JAM-C-deficient [having the JAM-C gene knocked out (KO)]

81 he major ligand for JAM-C, whereas homotypic JAM-C interactions remained at background levels.

82 we used function-blocking mAbs against human JAM-C to determine its role in human leukocyte adhesion

83 Our results identify JAM-C as a key regulator of polarized neutrophil TEM in

84 le JAM-C in fluid phase bound to immobilized JAM-C as assessed in a purified system; moreover, JAM-C-

85 NCI-H522 cells adhered to immobilized JAM-C, as well as to JAM-C-transfected CHO cells, but no

86 ter ovary (CHO) cells adhered to immobilized JAM-C.

87 This motif is conserved in JAM-C (Arg64-Ile65-Glu66), and a single amino acid mutat

88 Interestingly, JAM-C-blocking mAbs synergized with a combination of PEC

89 sion of JAM-C by infection with a lentivirus JAM-C GFP fusion protein did not increase adhesion or ex

90 ts reduced migration of normal and malignant JAM-C-expressing B cells to bone marrow, lymph nodes, an

91 RPE (hfRPE) with or without si-RNA mediated JAM-C knockdown and in adult native RPE wholemounts.

92 By immunofluorescence microscopy, JAM-C staining showed sparse localization to cell-cell j

93 mined the role of the cell adhesion molecule JAM-C, a protein known to mediate cellular polarity duri

94 Moreover, JAM-C was strongly up-regulated in the spontaneous early

95 as assessed in a purified system; moreover, JAM-C-transfected Chinese hamster ovary (CHO) cells adhe

96 We show that murine JAM-C is highly expressed on HSCs in the bone marrow (BM

97 y, anti-JAM-C antibodies blocked adhesion of JAM-C-expressing B cells to their ligand JAM-B, and immu

98 nal experiments revealed specific binding of JAM-C to CD11b/CD18 and provided evidence of other epith

99 vely, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for t

100 enhanced by blockade or genetic deletion of JAM-C in ECs.

101 ns further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated.

102 oxLDL treatment induced a disorganization of JAM-C localization that was no more restricted to the in

103 Strikingly, disruption of JAM-C function decreased basal permeability and prevente

104 erotic vessels revealed a high expression of JAM-C in association with neointimal smooth muscle cells

105 n, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the

106 identify the localization and expression of JAM-C, ZO-1, N-cadherin, and ezrin in cultures of human

107 orts on previously undetected expressions of JAM-C, namely on perineural cells, and in line with noci

108 We generated mice with inactivation of JAM-C.

109 Inclusion of JAM-C as a sole marker on lineage-negative BM cells yiel

110 The homophilic interaction of JAM-C can mediate tumor cell-endothelial cell interactio

111 Here, the homophilic interaction of JAM-C is presented and functionally characterized to med

112 The homophilic interaction of JAM-C was mediated by the isolated amino-terminal Ig dom

113 66R) abolished the homophilic interaction of JAM-C.

114 The level of JAM-C expression defines B-cell differentiation stages a

115 down decreases the S-palmitoylation level of JAM-C.

116 Desmosomal localization of JAM-C was further confirmed by experiments aimed at sele

117 Moreover, the loss of JAM-C expression resulted in stabilization of VE-cadheri

118 Overexpression of JAM-C by infection with a lentivirus JAM-C GFP fusion pr

119 ese results suggest that S-palmitoylation of JAM-C can be potentially targeted to control cancer meta

120 Palmitoylation of JAM-C promotes its localization to tight junctions and i

121 HUVEC revealed a large intracellular pool of JAM-C that showed little colocalization with von Willebr

122 e present study, we investigated the role of JAM-C in homing of human B cells, using a xenogeneic non

123 To determine the role of JAM-C in leukocyte retention in the RA synovium, in vitr

124 To investigate the role of JAM-C in neuronal functions further, mice with a specifi

125 Here, we investigated the role of JAM-C in oxidized low-density lipoprotein (LDL)-mediated

126 Our results highlight the novel role of JAM-C in recruiting and retaining leukocytes in the RA s

127 Here, the role of JAM-C in vascular permeability was investigated in vitro

128 point of regulation is the ubiquitylation of JAM-C by the E3 ligase Casitas B-lineage lymphoma (CBL),

129 f de novo AML patients at diagnosis based on JAM-C-expressing cells frequencies in the blood served a

130 ST fibroblasts and to RA ST was dependent on JAM-C.

131 AM-A but not those transfected with JAM-B or JAM-C.

132 hesion of NCI-H522 cells to JAM-C protein or JAM-C-transfected CHO cells was abolished in the presenc

133 Expression of related proteins JAM-C and CAR (Coxsackie and adenovirus receptor) was al

134 expression of JAM-A and the related proteins JAM-C, CAR, and AF-6 in the rabbit corneal endothelium.

135 itis (OA), and normal ST samples to quantify JAM-C expression.

136 dified LDL (eLDL) significantly up-regulated JAM-C on both HASMC and endothelial cells in a time- and

137 equivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and

138 ce with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated.

139 l cells was significantly blocked by soluble JAM-C or the isolated D1.

140 lls was abolished in the presence of soluble JAM-C or the isolated D1.

141 Recombinant soluble JAM-C in fluid phase bound to immobilized JAM-C as asses

142 is found in soluble form and whether soluble JAM-C (sJAM-C) mediates angiogenesis.

143 lung, whereas treatment of mice with soluble JAM-C prevented melanoma lung metastasis.

144 -C(-/-) mice as well as endothelial-specific JAM-C-deficient mice displayed significantly decreased B

145 Targeting JAM-C could thus constitute a new therapeutic strategy t

146 n the RA synovium and suggest that targeting JAM-C may be important in combating inflammatory disease

147 Recently, a JAM protein family member termed JAM-C was implicated in leukocyte adhesive interactions;

148 e that JAM-C defines HSCs in the BM and that JAM-C plays a role in controlling myeloid progenitor gen

149 These results demonstrate that JAM-C is a component of the autotypic junctional attachm

150 Here, we demonstrate that JAM-C is abundantly expressed basolaterally in intestina

151 Finally, we demonstrated that JAM-C controls Src family kinase (SFK) activation in LSC

152 These results provide evidence that JAM-C defines HSCs in the BM and that JAM-C plays a role

153 We found that JAM-C cotraffics with receptors associated with changes

154 We found that JAM-C is present in soluble form in normal serum and ele

155 l and electron microscopy, we show here that JAM-C is also expressed in peripheral nerves and that th

156 Our results show that JAM-C exists in soluble form and suggest that modulation

157 Here, we show that JAM-C expression defines a subset of leukemic cells endo

158 Here, we show that JAM-C undergoes S-palmitoylation on two juxtamembrane cy

159 These data suggest that JAM-C has a minimal role, if any, in PMN transmigration

160 nsepithelial migration and also suggest that JAM-C may play a role in desmosomal structure/function.

161 atic nerves from JAM-C-deficient [having the JAM-C gene knocked out (KO)] mice exhibited loss of inte

162 and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve

163 The underlying mechanisms of the JAM-C-mediated increase in endothelial permeability were

164 O cells or to CHO cells transfected with the JAM-C mutant (E66R).

165 SFK activation was uniquely found within the JAM-C-expressing LSC compartment.

166 Thus, JAM-C undergoes a homophilic interaction via the Arg64-I

167 adhered to immobilized JAM-C, as well as to JAM-C-transfected CHO cells, but not to mock-transfected

168 Adhesion of NCI-H522 cells to JAM-C protein or JAM-C-transfected CHO cells was abolish

169 core gene expression signature correlated to JAM-C expression that reveals LSC heterogeneity.

170 ion, and actin stress fiber formation due to JAM-C knockdown.

171 events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1.

172 Together, JAM-C represents a novel therapeutic target for melanoma

173 Taken together, JAM-C is up-regulated by oxLDL and may thereby contribut

174 ) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial

175 xLDL treatment of endothelial cells, whereas JAM-C on quiescent endothelial cells only mediates leuko

176 n the current study, we investigated whether JAM-C is found in soluble form and whether soluble JAM-C

177 f association of the Par6/Pals1 complex with JAM-C, thereby destabilizing apical ES to facilitate spe