ライフサイエンスコーパス: TSHR

1 TSHR Abs can be induced in mice by immunization, but stu

2 TSHR activation by TSH phosphorylates protein kinases AK

3 TSHR activation is initiated by binding of the hormone l

4 TSHR autoantibodies with TSH agonist or antagonist activ

5 TSHR cleavage at upstream site 1 (within amino acid resi

6 TSHR levels are 11-fold higher on thyrocytes than on TAO

7 TSHR mRNA also represents a new blood test to aid assess

8 TSHR mRNA provides an additional clinical tool for the e

9 TSHR mRNA was measured by quantitative RT-PCR from blood

10 TSHR rs12101255 and rs2268458 polymorphisms had no assoc

11 TSHR signaling overlaps with that of insulin-like grow f

12 TSHR-KO mice presented with developmental and growth del

13 TSHRs were not internalized by 30 min incubation with un

14 TSHRs, but not the closely related lutropin or follitrop

15 On chromosome 14, TSHR genetic variants in intron 1 could conceivably help

16 In this study, we generated a TSHR knockout (TSHR-KO) mouse by homologous recombinatio

17 embrane domain was defined by docking into a TSHR homology model and was supported by site-directed m

18 ary for trafficking to the cell surface of a TSHR with high affinity TSH binding similar to the wild-

19 sed TSH, a TSHR agonist, a cAMP analog, or a TSHR-stimulating antibody.

20 cells previously exposed to increased TSH, a TSHR agonist, a cAMP analog, or a TSHR-stimulating antib

21 ts of retrovirally-transduced mutant (A623I) TSHR or (Q227L) Galphas (GSP), using the rat thyroid cel

22 Moreover, Alexa546-TSH-activated TSHR internalization was not accompanied by Galpha(q) co

23 of ligand-independent, constitutively active TSHR abrogates osteoclast formation even under basal con

24 pport the concept of a constitutively active TSHR dimer or monomer that is naturally inhibited by the

25 ansfected with TSHR or constitutively active TSHR.

26 +/- 0.0014 for cells expressing TSHR alone, TSHR and L252P, or TSHR and C41S, respectively.

27 n ratios of flTSHR relative to two alternate TSHR mRNA splice variants.

28 this study, we compare levels of IGF-1R and TSHR on the surfaces of TAO and control orbital fibrobla

29 Moreover, IGF-1Rbeta and TSHR colocalize to the perinuclear and cytoplasmic compa

30 -3)), PDE4D (rs27178, p = 8.3 x 10(-3)), and TSHR (rs4903957, p = 8.6 x 10(-3)) loci.

31 , comprising disulfide-linked TSHR-alpha and TSHR-beta subunits, was required for the formation of TS

32 The association between EZH1 and TSHR mutations suggests a 2-hit model for the pathogenes

33 Co-expression of TSHR(GFP) and TSHR(Myc) constructs in Chinese hamster ovary cells resu

34 er in individually transfected TSHR(GFP) and TSHR(Myc):Cy3 cells cultured together and also by accept

35 inding kinetics for the TSH holoreceptor and TSHR ECD-GPI was obtained upon comparison of the TSH K(d

36 , efficacies, and specificities at LHCGR and TSHR.

37 tudies of the homologous residues in LHR and TSHR revealed both similarities and differences.

38 her invariant or highly conserved in LHR and TSHR.

39 y reports suggested that in TAO, both Tg and TSHR become overexpressed in orbital tissues.

40 nto pure CD34(+) and CD34(-) subsets, Tg and TSHR mRNA levels become substantially higher in CD34(+)

41 ) cells, express much lower levels of Tg and TSHR.

42 Ags, CHRNA1, GAD1, PLP1, KLK3, SAG, TG, and TSHR, was reduced.

43 brogated in compound TSHR-/-/TNFalpha-/- and TSHR+/-/TNFalpha+/- mice, respectively.

44 washing the cells to remove unbound TSH, and TSHR internalization by fluorescence microscopy using Al

45 This enhancement in TSHR-/- and TSHR+/- mice is abrogated in compound TSHR-/-/TNFalpha-/

46 The binding of TSH, as well as TSHR autoantibodies, induced time- and dose-dependent re

47 arious permutations of the four cysteines at TSHR positions 24, 29, 31, and 41 (signal peptide residu

48 the TSHR by stimulating TSHR autoantibodies (TSHR-Ab's) in Graves disease patients may provide a func

49 ps relative to 1.83 pmol/ml for controls) by TSHR-expressing Chinese hamster ovary cells.

50 ne, the serpentine region of the TSHR, or by TSHR dimerization.

51 he in vivo proliferative response to chronic TSHR stimulation relies heavily on the activation of the

52 /- and TSHR+/- mice is abrogated in compound TSHR-/-/TNFalpha-/- and TSHR+/-/TNFalpha+/- mice, respec

53 underlying molecular mechanism of decreased TSHR expression, we examined the methylation status of t

54 -dose A-subunit adenovirus failed to develop TSHR Abs, hyperthyroidism, or splenocyte responses to TS

55 ith high-dose A-subunit adenovirus developed TSHR Abs with thyrotropin-binding inhibitory activity, a

56 SHR A-subunit protein unexpectedly developed TSHR Abs, but only of the nonpathogenic variety detected

57 ing of the ligand into the three-dimensional TSHR model was experimentally confirmed.

58 In patients with DTC, elevated TSHR mRNA levels became undetectable in all patients (n

59 inuous segments almost completely eliminated TSHR cleavage at Site 1.

60 1, in contrast to TSH, was unable to enhance TSHR posttranslational cleavage.

61 inases in 2 cell lines engineered to express TSHRs, human embryonic kidney HEK-TSHR cells and human o

62 , and 0.0059 +/- 0.0014 for cells expressing TSHR alone, TSHR and L252P, or TSHR and C41S, respective

63 immunization with syngeneic cells expressing TSHR.

64 show that org41841 is a partial agonist for TSHR but with lower potency than for LHCGR.

65 The reference range and applications for TSHR mRNA were previously defined from 663 samples from

66 However, it may also provide decoys for TSHR antibodies, thus influencing their biological actio

67 o-acid specificity in a region important for TSHR cleavage (GQE367-369).

68 and AAM2R were immunologically distinct from TSHR antibodies.

69 een sites 1 and 2 could not be purified from TSHR epitope-tagged (c-myc) within this region.

70 lls, known as fibrocytes, express functional TSHR, infiltrate the orbit, and comprise a large subset

71 tibodies, NOD.H2(h4) mice with the human (h) TSHR (hTSHR) A-subunit transgene expressed in the thyroi

72 AKT1 in both cell types and of ERK1/2 in HEK-TSHR cells.

73 to express TSHRs, human embryonic kidney HEK-TSHR cells and human osteoblastic U2OS-TSHR cells.

74 Both heterozygotic and homozygotic TSHR null mice are osteopenic with evidence of enhanced

75 overed a small molecule that activates human TSHR in vitro, is orally active in mice, and could be a

76 BALB/c human TSHR A-subunit mice were bred to NOD.H2(h4) mice, and tr

77 hese agonists are highly selective for human TSHR versus other glycoprotein hormone receptors and int

78 overcome using high-dose, full-length human TSHR adenovirus.

79 free A-subunit rather than full-length human TSHR, the shed A-subunit appears to drive the disease-as

80 with a soluble extracellular domain of human TSHR (TBP), or TBP expressed on human embryonic kidney c

81 us demonstrate aberrant methylation of human TSHR as a likely molecular pathway responsible for the s

82 nses, spontaneously arising pathogenic human TSHR Abs cross-react poorly with the mouse TSHR and do n

83 We hypothesized that transferring the human TSHR A-subunit to NOD.H2(h4) mice would result in loss o

84 HEK-EM293 cells permanently expressing human TSHRs incubated with isobutylmethylxanthine for 30 min a

85 Chinese hamster ovary cells expressing human TSHRs using flow cytometry and enzyme-linked immunosorbe

86 As in humans, TSHR/NOD.H2(h4) female mice were more prone than male mi

87 The TSH-induced decrease in TSHR oligomers was found to be secondary to dissociation

88 This enhancement in TSHR-/- and TSHR+/- mice is abrogated in compound TSHR-/

89 ctable sodium-iodide symporter expression in TSHR-KO thyroid glands.

90 g the pre-existing pathogenic TSHR level, in TSHR/NOD.H2(h4) mice inactive hTSHR Ag injected without

91 Even a 50% reduction in TSHR expression produces profound osteoporosis (bone los

92 the dominant role of the H chain V region in TSHR recognition.

93 with A-subunit protein and adjuvants induced TSHR Abs lacking the characteristics of human autoantibo

94 t on TSHR cAMP signaling, dynasore inhibited TSHR cAMP signaling in the absence or presence of TSHR i

95 iously, in an induced mouse model, injecting TSHR A-subunit protein attenuated hyperthyroidism by div

96 thway of the mouse could be dissociated into TSHR-dependent and -independent steps.

97 Intrathymic TSHR expression was decreased in individuals homozygous

98 In this study, we generated a TSHR knockout (TSHR-KO) mouse by homologous recombination for use as a

99 tations were strongly associated with known (TSHR, GNAS) or presumed (adenylate cyclase 9 [ADCY9]) al

100 We found that hyperthyroid mice lacking TSHR had greater bone loss and resorption than hyperthyr

101 ormation in TG was decreased in mice lacking TSHRs.

102 roximately 50%) was evident in a chimeric LH-TSHR in which the juxtamembrane segment of the LHR (doma

103 bunit structure, comprising disulfide-linked TSHR-alpha and TSHR-beta subunits, was required for the

104 Single-chain, mature TSHR do exist on the cell surface.

105 wever, only TSHR-transgenic NOD.H2(h4) mice (TSHR/NOD.H2(h4)) developed pathogenic TSHR Abs as detect

106 subunit as opposed to a genetically modified TSHR that cleaves minimally into subunits.

107 1/2 (3.1+/-0.2-fold), whereas small molecule TSHR agonist C2 had no or little effect on pAKT1 (1.8+/-

108 s specifically inhibited by a small molecule TSHR antagonist.

109 n TSHR Abs cross-react poorly with the mouse TSHR and do not cause thyrotoxicosis.

110 In contrast, loss of function of a mutant TSHR (Pro --> Leu at 556) in congenital hypothyroid mice

111 terodimers with two binding-deficient mutant TSHRs, L252P and C41S.

112 d for radiolabeled TSH binding to the native TSHR and was able to compete for TSH-induced stimulation

113 ized mice developed autoantibodies to native TSHR by day 90 and, by day 180, showed considerable stim

114 hyroglobulin and thyroid-peroxidase, but not TSHR, Abs.

115 estigate disease pathogenesis and test novel TSHR Ag-specific immunotherapies aimed at curing Graves'

116 ective validation study tests the ability of TSHR mRNA to diagnose DTC preoperatively and to detect c

117 Functional characterization of TSHR mutants confirms the previously suggested close pro

118 ol-3-kinase signaling cascades downstream of TSHR is still controversial.

119 d that conformationally intact ectodomain of TSHR is sufficient for disease induction.

120 a more precise estimation of the effects of TSHR single nucleotide polymorphisms (SNPs) on GD/GO usi

121 , the same two SNPs located at the 5' end of TSHR showed the most significant association with spawni

122 HR gene expression and facilitates escape of TSHR-reactive T cells from central tolerance, triggering

123 Exposure of TSHR(GFP/Myc) cells to forskolin or cytochalasin D cause

124 In this report, we confirm the expression of TSHR in thymocytes by protein immunoblotting and quantit

125 Co-expression of TSHR(GFP) and TSHR(Myc) constructs in Chinese hamster ov

126 n in Western breeds and the near fixation of TSHR in all modern chickens took place only in the past

127 subunits, was required for the formation of TSHR dimers and higher order complexes.

128 Thyroid glands of TSHR-KO mice produced uniodinated thyroglobulin, but the

129 We propose that methylation of TSHR may provide a novel diagnostic marker of malignancy

130 sis of three-dimensional molecular models of TSHR and LHCGR predicted a binding pocket for org41841 i

131 tivation by demonstrating MS-1 modulation of TSHR function in vitro as evidenced by downregulation an

132 compound combined with prior mutagenesis of TSHR provided compelling experimental evidence in suppor

133 at TG processing in the secretory pathway of TSHR-hyperstimulated thyrocytes alters the structure of

134 evious studies demonstrating the presence of TSHR dimers and oligomers in thyroid tissue.

135 cAMP signaling in the absence or presence of TSHR internalization, and expression of a dominant-negat

136 pression of beta-arrestin-2 had no effect on TSHR cAMP signaling, dynasore inhibited TSHR cAMP signal

137 However, only TSHR-transgenic NOD.H2(h4) mice (TSHR/NOD.H2(h4)) develo

138 -gamma(-/-) mice developed EAGD with optimal TSHR-specific immune responses, while IL-4(-/-) mice com

139 ed specifically against either IGF-1Rbeta or TSHR bring both proteins out of solution.

140 essed with TSHR, that is, when TSHR/L252P or TSHR/C41S heterodimers could only bind one TSH, TSH-stim

141 ls expressing TSHR alone, TSHR and L252P, or TSHR and C41S, respectively.

142 These in vivo studies suggested a partial TSHR inactivation induced by excessive stimulation by MS

143 spontaneous, iodine-accelerated, pathogenic TSHR Abs in female mice, providing a unique model to inv

144 mice (TSHR/NOD.H2(h4)) developed pathogenic TSHR Abs as detected using clinical Graves' disease assa

145 rone than male mice to developing pathogenic TSHR Abs.

146 model that spontaneously develops pathogenic TSHR autoantibodies, NOD.H2(h4) mice with the human (h)

147 ated hyperthyroidism by diverting pathogenic TSHR Abs to a nonfunctional variety.

148 than attenuating the pre-existing pathogenic TSHR level, in TSHR/NOD.H2(h4) mice inactive hTSHR Ag in

149 nized only by nonpathogenic (not pathogenic) TSHR Abs.

150 We measured persistent TSHR signaling as an accumulation of cAMP in HEK-EM293 c

151 oplasms or suspicious cytology, preoperative TSHR mRNA >1 ng/mug had 96% predictive value for DTC, wh

152 17) in a region corresponding to the primary TSHR cleavage site, which has only one N-linked glycan.

153 ever, expression of beta-arrestin-2 promoted TSHR internalization that was inhibited by dynasore, a d

154 eptor tagged with green fluorescent protein (TSHR(GFP)) and expressed in a heterologous system was pr

155 h binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP).

156 to the thyroid-stimulating hormone receptor (TSHR) (TSAbs) that induce a sustained state of hyperthyr

157 nd the thyroid-stimulating hormone receptor (TSHR) are targets for autoantibody generation in the aut

158 Thyroid-stimulating hormone receptor (TSHR) expression is frequently silenced in epithelial th

159 of the thyroid stimulating hormone receptor (TSHR) gene with GD and GO have been studied in different

160 of the thyroid stimulating hormone receptor (TSHR) gene.

161 The thyroid stimulating hormone receptor (TSHR) is a G protein-coupled receptor (GPCR) with a char

162 The thyroid-stimulating hormone receptor (TSHR) is a G protein-linked, 7-transmembrane domain (7-T

163 d that thyroid-stimulating hormone receptor (TSHR) might be activated by org41841 also.

164 undred thyroid stimulating hormone receptor (TSHR) mutations, as well as cancer related mutations in

165 to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone r

166 Thyroid-stimulating hormone receptor (TSHR) plays a central role in regulating thyroid functio

167 The thyroid stimulating hormone receptor (TSHR) represents the primary autoantigen in GD, in which

168 R) and thyroid-stimulating hormone receptor (TSHR)) was expected to be similar.

169 as the thyroid-stimulating hormone receptor (TSHR), is the primary antigen of Graves disease.

170 es for thyroid-stimulating hormone receptor (TSHR), the SOX11 transcription factor (SOX11), calmoduli

171 elated thyroid-stimulating hormone receptor (TSHR), was fundamentally altered, and the resulting anal

172 Thyrotropin receptor (TSHR) Ab's of the stimulating variety are the cause of h

173 antibodies bind to the thyrotropin receptor (TSHR) and cause hyperthyroidism.

174 AAM2R with stimulating thyrotropin receptor (TSHR) antibodies was evaluated before and after adsorpti

175 e studied cell surface thyrotropin receptor (TSHR) by biotinylating proteins on the surface of metabo

176 rich N terminus of the thyrotropin receptor (TSHR) ectodomain and epidermal growth factor-like repeat

177 rculating DTC cells by thyrotropin receptor (TSHR) mRNA measurement distinguished benign from maligna

178 Abs that stimulate the thyrotropin receptor (TSHR), the cause of Graves' hyperthyroidism, only develo

179 The thyrotropin receptor (TSHR), the major autoantigen in Graves' disease, is post

180 dies that activate the thyrotropin receptor (TSHR).

181 b's) that activate the thyrotropin receptor (TSHR).

182 (TSAbs) activating the thyrotropin receptor (TSHR).

183 g to identify a small-molecule TSH receptor (TSHR) agonist that was modified to produce a second agon

184 -stimulating hormone (TSH) and TSH receptor (TSHR) and is indispensable for TSH/TSHR-mediated prolife

185 TSH receptor (TSHR) engagement stimulates the production of cyclic AMP

186 e resorption, mediated via the TSH receptor (TSHR) found on osteoblast and osteoclast precursors.

187 H binding to both sites of the TSH receptor (TSHR) homodimer, and TSH-stimulated IP1 production (EC(5

188 gative cooperativity) requires TSH receptor (TSHR) homodimerization, the latter involving primarily t

189 r persistent cAMP signaling by TSH receptor (TSHR) is dependent on internalization.

190 ions in the genes encoding the TSH receptor (TSHR) or the Gs protein alpha subunit (GNAS) are found i

191 cells defined by expression of TSH receptor (TSHR) using flow cytometry were selectively associated w

192 tropin (TSH) activation of the TSH receptor (TSHR), a 7-transmembrane-spanning receptor (7TMR), may h

193 vely active ligand-independent TSH receptor (TSHR).

194 into the thyrotropin hormone (TSH) receptor (TSHR) cleavage, we sought to convert the noncleaving lut

195 The thyrotropin (TSH) receptor (TSHR) is a member of the heterotrimeric G protein-couple

196 thyroid stimulating hormone (TSH) receptor (TSHR) with high affinity, inhibit labelled TSH binding t

197 ntibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured.

198 thyroid-stimulating hormone (TSH) receptor (TSHR), TSH negatively regulates osteoclast differentiati

199 thyroid-stimulating hormone (TSH)] receptor (TSHR) is known to acutely and persistently stimulate cAM

200 ction (thyroid-stimulating hormone receptor, TSHR).

201 on of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T3 toxic

202 y, our data alter current concepts regarding TSHR cleavage by suggesting limited (not absent) amino-a

203 ith a demethylating agent partially restored TSHR expression.

204 rrelation between thyroid function and serum TSHR-Ab concentrations.

205 ntibody has all the characteristics of serum TSHR autoantibodies.

206 gnition by TSAb of the holoreceptor, soluble TSHR A subunits (known to be shed from surface TSHR) ful

207 igen in autoimmune thyroid disease, and some TSHR antibodies may activate the receptor, while others

208 Stimulating TSHR antibodies are the cause of thyroid overstimulation

209 hus, inactivation of the TSHR by stimulating TSHR autoantibodies (TSHR-Ab's) in Graves disease patien

210 measured persistent signaling by stimulating TSHR-expressing human embryonic kidney-EM293 cells with

211 Due to its complex structure, TSHR appears to have unstable molecular integrity and a

212 us recombination for use as a model to study TSHR function.

213 s the first characterization of cell surface TSHR including their A and B subunits.

214 HR A subunits (known to be shed from surface TSHR) fully neutralized autoantibody-binding activity.

215 We previously demonstrated that TSHR, the target of this autoimmune response, is also a

216 rovided in vivo evidence, demonstrating that TSHR expression was required for expression of sodium-io

217 Furthermore, they indicate that TSHR levels on orbital fibroblasts are considerably lowe

218 n thyroid tumor cell lines, we observed that TSHR was normally expressed at the protein and mRNA leve

219 er (FRET) using tagged receptors showed that TSHR formed homodimers and heterodimers with two binding

220 We also showed that TSHR is, unexpectedly, expressed in thymocytes.

221 We suggest that TSHR coupling to phosphoinositide signaling is dependent

222 We conclude that TSHRs do not have to be internalized to exhibit persiste

223 tion, confirming once again our premise that TSHRs have a critical role in regulating bone remodeling

224 The TSHR is also a primary antigen in autoimmune thyroid dis

225 the former, was surprising because both the TSHR ECD and TSH holoreceptor contain the entire TSH-bin

226 served that the TSH binding affinity for the TSHR ECD-GPI was significantly lower than that for the T

227 To generate a structural model for the TSHR we applied an integrated structural biology approac

228 I-TSH dissociated much more rapidly from the TSHR ECD-GPI than from the TSH holoreceptor.

229 interaction involving a noncoding SNP in the TSHR gene that regulates thymic TSHR gene expression and

230 d distinct downstream cleavage site 2 in the TSHR.

231 Although early studies investigating the TSHR and GD proved inconclusive, more recently we provid

232 eplaced with the corresponding domain of the TSHR (residues 363-418).

233 by downregulation and desensitization of the TSHR at concentrations of MS-1 achieved in the in vivo s

234 Thus, inactivation of the TSHR by stimulating TSHR autoantibodies (TSHR-Ab's) in G

235 found to be secondary to dissociation of the TSHR complexes as evidenced by an increase in fluorescen

236 f the receptor can result in shedding of the TSHR ectodomain, providing a source of antigen and activ

237 n, we examined the methylation status of the TSHR gene promoter by sequencing bisulfite-treated DNA f

238 d to confirm the genetic associations of the TSHR gene with GD/GO.

239 s' disease, interact with this region of the TSHR in a manner critically dependent on antigen conform

240 This review discusses the role of the TSHR in the physiological and pathological stimulation o

241 ysteine (Cys) residues in this region of the TSHR on the functional response to TSAb in Graves' patie

242 d convincing evidence for association of the TSHR region with disease.

243 NPs, across an extended 800 kb region of the TSHR to refine association in a cohort of 768 GD subject

244 Of the TSHR variants detected, (6/7, 86%) were in benign nodule

245 ted that the less active conformation of the TSHR was comprised of receptor complexes and that such c

246 ue distance restraints within the ECD of the TSHR, its ligand TSH, and the hormone-receptor complex.

247 lasma membrane, the serpentine region of the TSHR, or by TSHR dimerization.

248 1.33-1.81), both located in intron 1 of the TSHR.

249 e for TSAb at the critical N terminus of the TSHR.

250 the glycoprotein hormone receptors, only the TSHR undergoes intramolecular cleavage into disulfide-li

251 more profound in cells that overexpress the TSHR than those transfected with empty vector.

252 ells that a mouse mAb (3BD10) recognized the TSHR ectodomain with a glycosidylphosphatidylinositol (E

253 igomeric forms by ligand binding returns the TSHR to an activated state.

254 MD in negative cooperativity, we studied the TSHR ECD tethered to the cell surface by a glycosylphosp

255 In summary, the TSHR/NOD.H2(h4) mouse strain develops spontaneous, iodin

256 A 50-amino acid insertion unique to the TSHR ectodomain (residues 317-366) plays no role in liga

257 ise the possibility that autoimmunity to the TSHR in humans may not involve epitopes on a cross-react

258 or amplifies the autoimmune response to the TSHR, thereby causing Graves disease in genetically susc

259 Hence, by using the TSHR-KO mouse, we provided in vivo evidence, demonstrati

260 he protein and mRNA level in cells where the TSHR gene was unmethylated, whereas it was silenced in c

261 reas it was silenced in cell lines where the TSHR promoter was hypermethylated.

262 cognized a conformational epitope within the TSHR alpha (or A) subunit but excluding the receptor cle

263 proximity of Ser-281 and Ile-486 within the TSHR.

264 g SNP in the TSHR gene that regulates thymic TSHR gene expression and facilitates escape of TSHR-reac

265 Using functional assays, we show that thymic TSHR is functional and that TSAbs can stimulate thymocyt

266 d translocation of beta-arrestin-1 and -2 to TSHR, whereas C2 failed to translocate either beta-arres

267 ulating hormone or the human autoantibody to TSHR.

268 port of computational models of 3 binding to TSHR and LHCGR within their transmembrane cores.

269 germline, which showed negligible binding to TSHR, indicating importance of somatic hypermutation in

270 labelled monoclonal autoantibody binding to TSHR.

271 uire a cross-reactive pathogenic response to TSHR.

272 hyperthyroidism, or splenocyte responses to TSHR Ag.

273 skewing of cytokine and immune responses to TSHR in favor of Th1 and Th2, respectively.

274 emonstrated that skewing immune responses to TSHR, using either Flt3-L or GM-CSF, in favor of Th1 or

275 ate and organify iodide could be restored to TSHR-KO thyroids when cultured in the presence of the ad

276 s dependent on binding 2 molecules of TSH to TSHR homodimer, causing a conformational change allowing

277 energy transfer in individually transfected TSHR(GFP) and TSHR(Myc):Cy3 cells cultured together and

278 receptor (TSHR) and is indispensable for TSH/TSHR-mediated proliferation of thyroid follicular cells

279 y identifies GLIS3 as a key regulator of TSH/TSHR-mediated thyroid hormone biosynthesis and prolifera

280 TBAb's]) also poorly recognize the wild-type TSHR relative to the ECD-GPI.

281 rovide the first evidence that the wild-type TSHR TMD influences ligand binding affinity for the ECD,

282 er than the same ectodomain on the wild-type TSHR, despite the far higher level of expression of the

283 ional activity comparable with the wild-type TSHR.

284 In U2OS-TSHR cells, TSH up-regulated pAKT1 (7.1+/-0.5-fold), p38

285 y HEK-TSHR cells and human osteoblastic U2OS-TSHR cells.

286 roglobulin antibodies, 96% with undetectable TSHR mRNA also had no evidence of cancer recurrence.

287 This effect was TSHR specific because spontaneously occurring autoantibo

288 sistent IP1 production was not affected when TSHR internalization was inhibited or enhanced.

289 C41S was expressed with TSHR, that is, when TSHR/L252P or TSHR/C41S heterodimers could only bind one

290 Whether TSHR is involved in the pathogenesis of thyroid-associat

291 ization of a monoclonal antibody (MS-1) with TSHR-stimulating activity.

292 previously reported association of AITD with TSHR and FCRL3.

293 When L252P or C41S was expressed with TSHR, that is, when TSHR/L252P or TSHR/C41S heterodimers

294 MS-1 is a hamster mAb with TSHR-stimulating activity.

295 FN-gamma(-/-) and IL-4(-/-) BALB/c mice with TSHR.

296 ch negative cooperativity did not occur with TSHR ECD-GPI-expressing cells.

297 ial (e.g., Yersinia) Abs cross-reactive with TSHR, eventually leading to TSAbs.

298 region, namely LHR-NET317-319 replaced with TSHR-GQE367-369, or by substitution of the same three am

299 paB binding to DNA in cells transfected with TSHR or constitutively active TSHR.

300 Chinese hamster ovary cells transfected with TSHR.