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 also underlie Graves' orbitopathy (G

5 TSHR autoantibodies with TSH agonist or antagonist activ

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

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

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

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

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

23 ansfected with TSHR or constitutively active TSHR.

24 +/- 0.0014 for cells expressing TSHR alone, TSHR and L252P, or TSHR and C41S, respectively.

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

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

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

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

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

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

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

32 , efficacies, and specificities at LHCGR and TSHR.

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

34 her invariant or highly conserved in LHR and TSHR.

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

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

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

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

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

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

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

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

43 HR/NOD.H2(h4) mice with the goal of blocking TSHR Ab development.

44 t protein, which is shed from membrane bound TSHR, expressed at low levels in the thyroid.

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

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

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

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

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

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

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

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

53 The enhanced TSHR Ab response following injected TSHR A-subunit prote

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

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

56 immunization with syngeneic cells expressing TSHR.

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

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

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

60 OD.H2(h4) model, enhancement is specific for TSHR Abs, with Abs to thyroglobulin and thyroid peroxida

61 and AAM2R were immunologically distinct from TSHR antibodies.

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

63 disease pathogenesis: development of Graves TSHR Abs is limited by the availability of A-subunit pro

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

65 c NOD.H2(h4) mice that express the human (h) TSHR A-subunit in the thyroid gland spontaneously develo

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

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

68 In HEK 293 cells overexpressing TSHRs (HEK-TSHR cells), we found that TSHR activation exhibits an "

69 at may allow the generation of potent highly TSHR-selective drugs, of potential value for the treatme

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

86 nt a mechanism to prevent overstimulation in TSHR-expressing cells.

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

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

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

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

91 However, because inhibiting TSHR downregulation with combined expression of a domina

92 enhanced TSHR Ab response following injected TSHR A-subunit protein-nanoparticles is reminiscent of t

93 Unexpectedly, in transgenic mice, injecting TSHR A-subunit-ITE nanoparticles (not ITE-nanoparticles

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

95 Intrathymic TSHR expression was decreased in individuals homozygous

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

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

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

99 ormation in TG was decreased in mice lacking TSHRs.

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

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

102 1/2 (3.1+/-0.2-fold), whereas small molecule TSHR agonist C2 had no or little effect on pAKT1 (1.8+/-

103 s specifically inhibited by a small molecule TSHR antagonist.

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

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

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

107 Nonpathogenic TSHR Abs (ELISA) were enhanced in transgenics and induce

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

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

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

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

112 d insights into the intramolecular course of TSHR activation at the ectodomain/TMD interface, includi

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

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

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

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

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

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

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

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

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

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

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

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

125 nt a mechanism to prevent overstimulation of TSHR-expressing cells.

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

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

128 n at high TSH doses, we studied the roles of TSHR downregulation and of G(i)/G(o) proteins.

129 Stimulation of TSHR leads to increasing cAMP production that has been r

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

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

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

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

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

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

136 In HEK 293 cells overexpressing TSHRs (HEK-TSHR cells), we found that TSHR activation ex

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

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

139 yroid gland spontaneously develop pathogenic TSHR autoantibodies resembling those in patients with Gr

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

141 rone than male mice to developing pathogenic TSHR Abs.

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

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

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

145 cent of the transient increase in pathogenic TSHR Abs following the release of thyroid autoantigens a

146 ed and accelerated development of pathogenic TSHR Abs in hTSHR/NOD.

147 d and enhanced the development of pathogenic TSHR Abs measured by inhibition of TSH binding to the TS

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

165 to the thyroid-stimulating hormone receptor (TSHR) that act as agonists and induce excessive thyroid

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

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

168 nd the thyroid-stimulating hormone receptor (TSHR), stimulation with a drug-like agonist (E2) of the

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

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

171 s stimulated by TSH activating its receptor (TSHR), which upregulates the activity of many thyroid ge

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

173 ound ectodomain of the thyrotropin receptor (TSHR) activates the transmembrane domain (TMD) indirectl

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

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

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

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

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

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

180 dies that activate the thyrotropin receptor (TSHR).

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

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

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

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

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

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

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

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

189 tion involving coupling of the TSH receptor (TSHR) to Gs at low TSH doses and to G(i/o) at high TSH d

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

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

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

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

194 The thyrotropin (TSH) receptor (TSHR) signals via G proteins of all four classes and bet

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

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

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

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

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

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

201 ith a demethylating agent partially restored TSHR expression.

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

203 ntibody has all the characteristics of serum TSHR autoantibodies.

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

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

206 Stimulating TSHR antibodies are the cause of thyroid overstimulation

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

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

209 une system and the generation of stimulatory TSHR Abs in genetically predisposed individuals.

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

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

212 e findings emphasize the need for sufficient TSHR A-subunit protein to activate the immune system and

213 mU/ml) caused a 33% decrease in cell-surface TSHR.

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 essing TSHRs (HEK-TSHR cells), we found that TSHR activation exhibits an "inverted U-shaped dose-resp

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 that this biphasic cAMP response allows the TSHR to mediate responses at lower levels of TSH and tha

226 of other G protein-coupled receptors, as the TSHR has a uniquely large N-terminal ectodomain that inc

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

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

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

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

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

232 n ectodomain and transmembrane domain in the TSHR, as well as the transfer of activation to the trans

233 hibition of PAM-C2-activation by S37a in the TSHR-TMD construct lacking the ectodomain.

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

235 intramolecular activation mechanisms of the TSHR appear to be distinct from those of other G protein

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

237 and (d) is not involved in activation of the TSHR by E2.

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

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

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

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

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

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

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

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

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

247 ulation with a drug-like agonist (E2) of the TSHR, and structural homology modeling to unravel the fu

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

249 1.33-1.81), both located in intron 1 of the TSHR.

250 both TSH- and PAM-induced activation of the TSHR.

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

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

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

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

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

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

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

258 measured by inhibition of TSH binding to the TSHR.

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

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

261 terface and indicate an interaction with the TSHR-specific residues E404 (preceding IA) and H478 (ECL

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

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

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

286 This effect was TSHR specific because spontaneously occurring autoantibo

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

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

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

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

291 previously reported association of AITD with TSHR and FCRL3.

292 molecule, injected nanoparticles coated with TSHR A-subunit protein enhanced and accelerated developm

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

294 n-like growth factor 1 receptor (IGF1R) with TSHR autoantibodies, causing retro-orbital tissue expans

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

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

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

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

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

300 Chinese hamster ovary cells transfected with TSHR.