ライフサイエンスコーパス: GC-C

1 GC-C activity can regulate colonic cell proliferation by

2 GC-C and GC-CD853A showed similar Bmax and Kd values for

3 GC-C is also expressed in neurons, where it plays a role

4 GC-C is glycosylated in the extracellular domain, and di

5 GC-C is primarily expressed in the gastrointestinal trac

6 GC-C is targeted by the enterotoxigenic Escherichia coli

7 GC-C mRNA and protein were ectopically expressed in appr

8 GC-C mRNA was detected in blood mononuclear cells from a

9 GC-C null mice contained no detectable GC-C protein.

10 GC-C regulates ion and fluid secretion in the gut via cG

11 GC-C signaling regulated proliferation by restricting th

12 GC-C+/+ control mice or those having GC-C genetically ab

13 GC-C-/- mice had an increase in C. rodentium bacterial l

14 GC-C-deficient mice given the lactose diet reacted with

15 olon carcinoma cell (approximately 20 to 200 GC-C transcripts/cell) in 10(6) to 10(7) mononuclear blo

16 this model of osmotic diarrhea results in a GC-C-independent increase in intestinal fluid accumulati

17 ce or those having GC-C genetically ablated (GC-C-/-) were administered C. rodentium by orogastric ga

18 nce we focus on linaclotide, a 14-amino acid GC-C agonist with very low oral bioavailability that act

19 gesic mechanism of linaclotide: it activates GC-C expressed on mucosal epithelial cells, resulting in

20 n glycosylation at the same sites that allow GC-C to fold and bind ligand.

21 on isotope ratio mass spectrometry analysis (GC-C-IRMS).

22 By immunoblot analysis, GC-C protein appeared as early as 4 h after partial hepa

23 were characterized in uninfected GC-C+/+ and GC-C-/- mice using 16S rRNA PCR analysis.

24 Using 0.5 microg of total RNA and GC-C-specific primers, nested RT-PCR detected a single h

25 These results suggest the utility of STa and GC-C for the development of novel targeted imaging and t

26 ine the levels of guanylin, uroguanylin, and GC-C in mice with osmotic diarrhea.

27 to predict the primary interactions between GC-C agonists and their receptor.

28 nduction of guanylin and uroguanylin in both GC-C heterozygous and null animals.

29 ells were assayed for the expression of both GC-C and other epithelial cell-specific markers.

30 Immunoblot confirmed that both GC-C and GC-CD853A formed similar higher order oligomers

31 ild-type and heterozygous suckling mice, but GC-C null animals were resistant.

32 ' stage D colorectal cancer were analyzed by GC-C-specific nested RT-PCR using 1 microg of total RNA.

33 , purification, and halogenation followed by GC-C-IRMS analysis.

34 The recorded delta(15)N value by GC-C-IRMS was within the error of that of the underivati

35 inoma cells that express guanylyl cyclase C (GC-C) and SW480 human colon carcinoma cells that do not

36 Mutations in receptor guanylyl cyclase C (GC-C) cause severe gastrointestinal disease, including m

37 Guanylyl cyclase C (GC-C) has been shown to be the primary receptor involved

38 Guanylyl cyclase C (GC-C) is a multidomain, membrane-associated receptor gua

39 Guanylyl cyclase C (GC-C) is a transmembrane receptor expressed by human int

40 Guanylate cyclase C (GC-C) is a transmembrane receptor that is expressed prim

41 Guanylate Cyclase C (GC-C) is an apically-oriented transmembrane receptor tha

42 Guanylyl cyclase C (GC-C) is expressed in intestinal epithelial cells and se

43 Guanylyl cyclase C (GC-C) is the receptor for the heat-stable enterotoxin pr

44 uenced GUCY2C, encoding guanylate cyclase C (GC-C), an intestinal receptor for bacterial heat-stable

45 Guanylyl cyclase C (GC-C), an intestine-specific tumor suppressor, may repre

46 a selective agonist of guanylate cyclase C (GC-C), for SSc patients with refractory lower GI disease

47 STaR, also known as guanylyl cyclase C (GC-C), is a member of the transmembrane guanylyl cyclase

48 n binds to and activates guanylyl cyclase C (GC-C), regulating fluid and electrolyte secretion in int

49 in intestinal receptor guanylate cyclase C (GC-C), the genetic cause for the majority of CSD is stil

50 Guanylyl cyclase C (GC-C), the receptor for diarrheagenic enterotoxins and t

51 ng mutations in receptor guanylyl cyclase C (GC-C), the target of gastrointestinal peptide hormones g

52 me intestinal receptor, guanylate cyclase C (GC-C).

53 nd bind to the receptor guanylate cyclase C (GC-C).

54 al analgesic effects of guanylate cyclase-C (GC-C) agonists.

55 heir actions through the guanylyl cyclase-C (GC-C) receptor.

56 activates the receptor guanylate cyclase-C (GC-C) to reduce food intake and prevent obesity.

57 variation in mammalian guanylate cyclase-C (GC-C), an intestinal receptor targeted by bacterially en

58 enterotoxins (ST) bind guanylate cyclase-C (GC-C), resulting in fluid homeostasis or diarrhea, respe

59 alytic domain (D853A) of guanylyl cyclase-C (GC-C), the heat-stable enterotoxin (STa) receptor, rende

60 umably by activation of guanylate cyclase-C (GC-C), which stimulates production and release of cyclic

61 the intestinal receptor guanylate cyclase-C (GC-C).

62 tinal brush border, guanylyl cyclase type C (GC-C).

63 cose homeostasis are not mediated by central GC-C receptors.

64 A gas chromatograph-combustion (GC-C) system is described for the introduction of sample

65 However, under the same conditions, GC-C mRNA was detected in mononuclear cells from all 24

66 Relative to wild-type controls, GC-C(-/-) and Gn(-/-) mice had reduced apoptosis and inc

67 the human membrane receptor guanylyl cyclase GC-C in complex with Hsp90 and its co-chaperone Cdc37, p

68 a-stimulated cGMP accumulation by decreasing GC-C activation in intact T84 human colorectal carcinoma

69 GC-C null mice contained no detectable GC-C protein.

70 The newly developed GC-C-IRMS method was applied to modern plant protein and

71 Although they did not develop diarrhea, GC-C-sufficient and -deficient mice on the lactose diet

72 Here, eliminating GC-C expression in mice increased crypt length along a d

73 stion-isotope ratio mass spectrometry (EPCon-GC-C-IRMS).

74 not into normal tissues that do not express GC-C.

75 lung tumor xenografts, which do not express GC-C.

76 o human colon cancer xenografts that express GC-C but not into normal tissues that do not express GC-

77 P production in those transiently expressing GC-C but not GC-CD853A.

78 ells infected with vaccinia virus-expressing GC-C and GC-CD853A (VVGC-CD853A) had [125I]STa-binding c

79 ependent manner in vaccinia virus-expressing GC-C-infected cells but not in those infected with VVGC-

80 Familial GC-C mutations demonstrate that epithelial cGMP signalin

81 For GC-C-IRMS determinations, implementation of a two-point

82 therefore, identify downstream effectors for GC-C that contribute to regulating intestinal cell proli

83 of Cdx2, a transcription factor required for GC-C expression.

84 ss of ligand expression, suggests a role for GC-C in organizing the crypt-villus axis.

85 These findings demonstrate a novel role for GC-C signaling in facilitating mucosal wounding and infl

86 were performed with intestinal mucosae from GC-C knockout (KO) and wild type (WT) mice.

87 mammals, the pressure to retain a functional GC-C in the face of diarrhea-inflicted mortality remains

88 GC-C+/+ control mice or those having GC-C genetically ablated (GC-C-/-) were administered C.

89 and GC activity between mouse GC-C and human GC-C.

90 dels, assuming that murine GC-C mimics human GC-C in its biochemical properties and downstream signal

91 When glycosylation of human GC-C was prevented, either by pharmacological interventi

92 urine GC domain was lower than that of human GC-C, and allosteric regulation of the receptor by ATP b

93 ffinity of mouse GC-C for ligands than human GC-C.

94 specificity of a GC inhibitor towards human GC-C.

95 Our aim was to determine if GC-C is required for host defense during infection by th

96 dependence showed that (125)I-STa-binding in GC-C KO mice involved a receptor distinct from that of W

97 stimulated a significant increase in DBS in GC-C KO mice.

98 ated duodenal bicarbonate secretion (DBS) in GC-C KO mice in vitro and in vivo.

99 C+/+ mice and, to an even greater degree, in GC-C-/- animals.

100 in contrast, continued to cause diarrhea in GC-C null mice, demonstrating that the cAMP signaling pa

101 a (RELMbeta) was substantially diminished in GC-C(-/-) mice.

102 Moreover, crypt expansion in GC-C(-/-) mice was associated with adaptive increases in

103 on strongly decreased guanylin expression in GC-C+/+ mice and, to an even greater degree, in GC-C-/-

104 of each of the 10 sites of glycosylation in GC-C, either singly or in combination, identified two si

105 n led to significant liver histopathology in GC-C-/- mice as well as lymphocyte infiltration and elev

106 ell apoptosis was significantly increased in GC-C-/- mice following 10 days of infection and this was

107 lpha and IFN-gamma production was minimal in GC-C(-/-) animals.

108 nic mucosa were significantly less severe in GC-C(-/-) mice and moderately reduced in Gn(-/-) animals

109 Increased GC-C signaling disturbs normal bowel function and appear

110 e thought to be restricted to the intestine, GC-C mRNA has recently been detected in other tissues.

111 lation of recombinant RELMbeta by enema into GC-C(-/-) mice restores sensitivity to DSS-mediated muco

112 We showed that 131- and 140-kDa GC-C isoforms represented immature and mature GC-C glyco

113 inducing cell cycle arrest, and mice lacking GC-C display increased cell proliferation in colonic cry

114 t tracer studies indicated that mice lacking GC-C, unlike GC-C+/+ animals, had a substantial loss of

115 C-C isoforms represented immature and mature GC-C glycoforms on the basis of endoglycosidase H and PN

116 tructs of various domains of human and mouse GC-C to show that the extracellular domain of mouse GC-C

117 nding affinity and GC activity between mouse GC-C and human GC-C.

118 show that the extracellular domain of mouse GC-C contributed to log-orders lower affinity of mouse G

119 ibuted to log-orders lower affinity of mouse GC-C for ligands than human GC-C.

120 and [(2)H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on M

121 enerating liver contained four times as much GC-C as purified hepatocytes.

122 eclinical mouse models, assuming that murine GC-C mimics human GC-C in its biochemical properties and

123 We carried out functional studies of mutant GC-C using HEK293T cells.

124 Relative to naive GC-C+/+ mice, the commensal microflora load in uninfecte

125 f this study were to determine whether a non-GC-C receptor exists for STa and what is the functional

126 r, our results suggest that alternative, non-GC-C, receptors likely exist for STa, uroguanylin, and g

127 aimed to determine the genetic cause for non-GC-C non-syndromic CSD in 18 patients from 16 unrelated

128 Activation of GC-C by administration of ST to wild type, but not Gucy2

129 We investigated whether activation of GC-C by the endogenous agonist uroguanylin or the primar

130 Activation of GC-C by the endogenous ligands guanylin or uroguanylin e

131 Ligand activation of GC-C causes it to produce cyclic GMP inside target cells

132 Activation of GC-C elevates intracellular cGMP, which modulates intest

133 Agonists of GC-C are US Food and Drug Administration-approved drugs

134 ese data suggest that endogenous agonists of GC-C, such as uroguanylin, may play a role in regulating

135 Our phylogenetic and functional analysis of GC-C supports long-standing evolutionary conflict with d

136 at work as either agonists or antagonists of GC-C, and vaccines for the bacterial heat-stable enterot

137 o the mechanism of Cdc37 mediated binding of GC-C to the Hsp90 regulatory complex.

138 Chronic deregulation of GC-C activity in early life increases susceptibility to

139 to < or = 0.8 microg eliminated detection of GC-C and other tissue-specific transcripts in blood of h

140 ctively binds to the extracellular domain of GC-C with subnanomolar affinity.

141 The downstream effector of GC-C, cGMP, was released after administration of linaclo

142 The cytostatic effects of GC-C agonists were associated with accumulation of intra

143 The exuberant expression of GC-C by nonparenchymal cells and, to a lesser extent, he

144 Virus-mediated expression of GC-C in H295R cells revealed concentration-dependent STa

145 he present studies examine the expression of GC-C in normal tissues and tumors from esophagus and sto

146 estinal metaplasia and ectopic expression of GC-C.

147 deoxycholate and acid induced expression of GC-C.

148 urrent work on the physiological function of GC-C in the intestine.

149 dine-2,4,6-trione; BPIPP} as an inhibitor of GC-C that can suppress STa-stimulated cGMP accumulation

150 Ala(15) comprise the primary interactions of GC-C agonists with the receptor surface.

151 ivity and/or glycan-mediated interactions of GC-C may have a crucial role to play in its functions in

152 occurred in the proximal small intestines of GC-C KO and WT mice.

153 In the context of uniform loss of GC-C signaling during tumorigenesis, dysregulation of th

154 ve mutations in NHE3, a downstream target of GC-C, as a cause of CSD and implies primary basal NHE3 m

155 reflected low-level ectopic transcription of GC-C in CD34+ progenitor cells.

156 Guanylate cyclase C (GUCY2C or GC-C) and its ligands, guanylin (GUCA2A or Gn) and urogu

157 ed agonist of guanylate cyclase-C (GUCY2C or GC-C) that reduces symptoms associated with irritable bo

158 in membranes from COS7 cells overexpressing GC-C but not GC-CD853A.

159 -combustion-isotope ratio mass spectrometry (GC-C-IRMS) based method was developed and applied for an

160 -combustion-isotope ratio mass spectrometry (GC-C-IRMS) for the analysis of (15)N-enriched amino suga

161 -combustion-isotope ratio mass spectrometry (GC-C-IRMS) for the analysis of key volatile compounds sa

162 -combustion-isotope ratio mass spectrometry (GC-C-IRMS), to further contribute to the understanding o

163 tope ratio mass spectrometry method (HS-SPME-GC-C-IRMS) was developed to measure the carbon isotopic

164 fied as a target of E. coli enterotoxin STa, GC-C is an important regulator of physiological salt and

165 , was found to express linaclotide's target, GC-C.

166 Therapeutic strategies targeting GC-C are tested in preclinical mouse models, assuming th

167 clinical evidence supports the concept that GC-C agonists act as peripherally acting visceral analge

168 his work demonstrates the novel finding that GC-C signaling is an essential component of host defense

169 Given that GC-C is a major intestinal receptor in all mammals, the

170 Murine models indicate that GC-C regulates the composition of intestinal commensal m

171 In bats, we further show that GC-C diversification has sparked compensatory mutations

172 We also show that GC-C is the first identified receptor client of the lect

173 These results suggest that GC-C agonists like linaclotide alleviate colorectal pain

174 nses in migration and apoptosis suggest that GC-C coordinates component processes maintaining homeost

175 These data suggest that GC-C may be useful for detecting circulating colorectal

176 The GC-C gene was disrupted by insertion of neo into exon 1

177 relevance of genetic variants affecting the GC-C-CFTR pathway to conditions such as Crohn's disease

178 acetate derivatives of amino sugars for the GC-C-IRMS analysis of (15)N-enriched amino sugars in ter

179 16-fold higher in wild-type mice than in the GC-C null mice, and STa-stimulable guanylyl cyclase acti

180 e also carefully phenotyped mice lacking the GC-C receptor and found them to have normal body weight,

181 mechanisms by which GC-C agonists target the GC-C/cyclic guanosine-3',5'-monophosphate (cGMP) pathway

182 Therapeutic GC-C ligands are used to successfully treat constipation

183 Therefore, GC-C ligands may be novel therapeutic agents for the tre

184 Therefore, GC-C likely provides a protective effect against stresso

185 Thus, GC-C agonists regulate the proliferation of intestinal c

186 Thus, GC-C is the major cyclase activity present in the intest

187 the related peptide ligand guanylin bind to GC-C and stimulate an increase in cyclic GMP, inducing c

188 88, an inactive analog that does not bind to GC-C, did not selectively accumulate in cancer xenograft

189 colon cancer xenografts reflected binding to GC-C because (99m)Tc-NC100588, an inactive analog that d

190 (5--18) selectively recognizes and binds to GC-C expressed by human colon cancer cells in vivo.

191 odentium bacterial load in stool relative to GC-C+/+.

192 ing the regenerative period, we detected two GC-C isoforms that differed in their size, temporal expr

193 central nervous system administration of two GC-C agonists and found no significant reduction of food

194 al bacteria were characterized in uninfected GC-C+/+ and GC-C-/- mice using 16S rRNA PCR analysis.

195 the commensal microflora load in uninfected GC-C-/- mice was decreased and bacterial composition was

196 ies indicated that mice lacking GC-C, unlike GC-C+/+ animals, had a substantial loss of intestinal ba

197 e aim of this study was to determine whether GC-C and its ligands direct the course of intestinal inf

198 Here we discuss the mechanisms by which GC-C agonists target the GC-C/cyclic guanosine-3',5'-mon