ライフサイエンスコーパス: smoothen

1 rafficking of fibrocystin, polycystin-2, and smoothened.

2 n with ciliary accumulation of patched-1 and Smoothened.

3 nsitivity: cyp26b1, gata3, pdgfra, smad5 and smoothened.

4 t have been developed target the Hh receptor Smoothened.

5 h signaling pathway components downstream of Smoothened.

6 ain and TMD stabilizes the inactive state of Smoothened.

7 identify EHD1 as a direct binding partner of Smoothened.

8 that cholesterol itself binds and activates Smoothened.

9 erol and the mechanism by which it regulates Smoothened.

10 edgehog (Shh) 2.02-fold, patched1 1.58-fold, smoothened 3.54-fold, glioma-associated oncogene homolog

11 pment act by binding to a common site within Smoothened, a critical pathway component.

12 of the Hh signal transducer and oncoprotein Smoothened, a GPCR that contains two distinct ligand-bin

13 pamine action in binding to and antagonizing Smoothened, a membrane transductory component.

14 Conditional deletion of smoothened, a molecule necessary for responsiveness to I

15 and homeostasis by alleviating repression of Smoothened, a seven-pass transmembrane protein.

16 signaling mitigated tumor progression in the smoothened A1 (SmoA1) transgenic MB mouse.

17 Similarly, Smoothened accumulates in cilia on cells mutated for BBS

18 NPP5E restored TZ molecular organization and Smoothened accumulation at cilia.

19 of the binding site, which is sufficient for Smoothened activation and is unique among CRD-containing

20 n the bilayer is sufficient for constitutive Smoothened activation.

21 We propose that the endogenous Smoothened activator is cholesterol, not oxysterols, and

22 Patched-1 (Ptch1), which, in turn, regulates Smoothened activity (canonical Hh signaling) as well as

23 l and physiology-based approaches to monitor Smoothened activity in cellular and in vitro contexts.

24 naling with recombinant human SHH (rhShh) or smoothened agonist (SAG) increased levels of Ptch1, Gli1

25 Administration of Shh mimetic, smoothened agonist (SAG) restored BBB integrity and also

26 this study, humanized mice were treated with Smoothened Agonist (SAG), a Sonic Hedgehog (Shh) mimetic

27 mouse iPSCs treated with retinoic acid and a smoothened agonist differentiated into motoneurons expre

28 ion of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or n

29 hrough expression of a constitutively active Smoothened allele in mice gives rise to aggressive skele

30 the G-protein-coupled transmembrane protein Smoothened, an activating component, is present in limit

31 postnatal astrocytes by targeted removal of Smoothened, an obligate Shh coreceptor, resulted in upre

32 edgehog signaling requires sterol binding to Smoothened and define key residues for sterol recognitio

33 SC activation by influencing the activity of Smoothened and GLI2, suggesting TB4 as a novel therapeut

34 followed by the decreased expression of both smoothened and GLI2.

35 the primary cilium-associated trafficking of Smoothened and Hedgehog signaling.

36 BBS genes in mice result in accumulation of Smoothened and Patched 1 in cilia and have a decreased S

37 Wild-type Smoothened and physiological Hedgehog patterning were no

38 oteins to the cilium, including Arl13b, AC3, Smoothened and Pkd2.

39 that encodes the Hedgehog pathway activator Smoothened and the Notch pathway genes Notch, presenilin

40 ple Hedgehog components including Patched-1, Smoothened, and Gli2, and fail to activate the pathway u

41 ntegrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase

42 eam from the membrane receptors, Patched and Smoothened, and the primary cilium.

43 the essential downstream pathway component, Smoothened, and to limit the range of signaling by seque

44 uh-7 cells were reversed by LDE225, a potent Smoothened antagonist.

45 Smoothened antagonists directly target the genetic basis

46 establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and

47 in cases where tumors acquire resistance to Smoothened antagonists, and also in cases where signalin

48 ered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable B

49 n resulted in the discovery of high affinity Smoothened antagonists, one of which was further profile

50 by mechanisms distinct from that of current Smoothened antagonists, retain inhibitory activity in vi

51 genetic lesions rendering them resistant to Smoothened antagonists.

52 umors with emerged or a priori resistance to Smoothened antagonists.

53 n parallel with phosphorylation to stabilize Smoothened, antagonizing its ubiquitination and subseque

54 Drosophila lipoproteins and act directly on Smoothened at physiological concentrations to repress si

55 say revealed that TB4 interacted with either smoothened at the cytoplasm or GLI2 at the nucleus in LX

56 ty is required at the level or downstream of Smoothened but upstream of the transcription activator G

57 ndently of Shh and the transmembrane protein Smoothened, but it is dependent on the transcription fac

58 ly by modulating the activity of Patched and Smoothened, but results have been conflicting.

59 the Shh ligand and the transmembrane protein Smoothened, but upstream of the Gli2 transcription facto

60 Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich d

61 that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol.

62 a(+) gradient common to metazoans, regulates Smoothened by shielding its heptahelical domain from cho

63 ollaborative effort, wherein synthesizing a "smoothened" cholesterol analogue would provide a direct

64 the ciliary localization of proteins (e.g., Smoothened) containing signals that normally facilitate

65 Patched1-Smoothened coupling is rapid, dynamic, and can be recapi

66 n, a region that is dispensable for Patched1-Smoothened coupling.

67 T20, GMAP210, and the exocyst complex, while smoothened delivery is largely independent of these comp

68 suppressing fatty acid oxidation (FAO), in a smoothened-dependent manner.

69 uctural and biochemical characterizations of Smoothened domains have begun to unlock this riddle, how

70 despite the connectivity of the network the smoothening effect of surface tension on the imbibition

71 flux trajectory consequently has a dramatic smoothening effect, and the resulting surfaces appear in

72 cts occur independently of the lipid-binding Smoothened extracellular domain, a region that is dispen

73 cle for coordinated removal of patched-1 and Smoothened from cilia during hedgehog signaling.

74 of Shh pathway (Gli1, Gli2, Patched1/2, and Smoothened), Gli targets (Bcl-2, XIAP and Cyclin D1), an

75 f primary HSCs, with decreased expression of smoothened, GLI2 and ILK compared with cells transfected

76 Small molecules targeting MEK1/2 and Smoothened hamper proliferation in EphA2-deficient cells

77 signal-transducing component of the pathway, Smoothened, has revealed itself to be an efficacious the

78 Hedgehog/Smoothened (Hh/Smo) signaling has been variably proposed

79 nes encoding patched homologue 1 (PTCH1) and smoothened homologue (SMO), occur in basal-cell carcinom

80 conditional hepatocyte-specific deletion of Smoothened in adult mice, we showed that hepatocellular

81 Dex antagonizes Shh signaling downstream of Smoothened in medulloblastoma.

82 lly requires extracellular Na(+) to regulate Smoothened in our assays, raising the possibility that a

83 cilium, had reduced ciliary concentration of Smoothened in response to Sonic hedgehog stimulation, an

84 dly, we find a cholesterol molecule bound to Smoothened in the CRD binding site.

85 deleting Sonic hedgehog (Shh) in neurons or Smoothened in the epidermis demonstrates that Shh is an

86 1 protein co-localizes with the SHH receptor Smoothened in the primary cilia upon ligand stimulation.

87 localization of the receptors patched-1 and Smoothened in the primary cilium.

88 By reconstituting purified Smoothened in vitro, we show that cholesterol within the

89 cted by IPI-926, suggesting the existence of smoothened-independent Gli activation in this model.

90 l proliferation and Gli-1 activation through Smoothened-independent non-canonical signaling.

91 exhibited marked chromosomal instability and Smoothened-independent upregulation of Cyclin B1, a puta

92 e UPR agonist thapsigargin attenuated mutant Smoothened-induced phenotypes in vivo in Drosophila mela

93 ch mesenchymal cells, antagonists of WNT and Smoothened inhibited gastrin-induced proliferation and W

94 ched following anti-mitotic chemotherapy and Smoothened inhibition, creating a reservoir for tumor re

95 ed drug-resistant tumor variants that bypass Smoothened inhibition.

96 f IPF fibroblasts was partially resistant to Smoothened inhibition.

97 Importantly, smoothened inhibitor treatment ameliorated metachondroma

98 The SMOOTHENED inhibitor vismodegib is FDA approved for adva

99 nevus (Gorlin) syndrome indicating that the smoothened inhibitor vismodegib reduces basal-cell carci

100 a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inhibitor, blocks this effect and inhibits gr

101 In cultured cells, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expres

102 recapitulated in control mice treated with a Smoothened inhibitor.

103 Smoothened inhibitors (SIs) are a new type of targeted t

104 However, resistance to Smoothened inhibitors occurs by genetic changes of Smoot

105 effectiveness and FDA approval of the first Smoothened inhibitors validates this class of agents, bu

106 t respond to therapeutic strategies, such as smoothened inhibitors, that target upstream components o

107 is and the emerging clinical experience with smoothened inhibitors.

108 s, a tight biochemical and physical coupling smoothens initial primer-caused heterogeneities and gove

109 embranes and affects retrograde transport of Smoothened inside cilia.

110 protein-coupled receptor (GPCR)-like protein Smoothened into cilia and culminates in gene transcripti

111 onditions, EHD1 was shown to co-traffic with Smoothened into the developing primary cilia and we iden

112 The Hedgehog signal transducer Smoothened is structurally similar to G protein-coupled

113 tment of TZ scaffolding proteins and reduced Smoothened levels at cilia.

114 Suppressor of Fused and Smoothened localize to the cilium through an IFT122-inde

115 of the Hedgehog signal transduction protein Smoothened (LysMCre/Smo(KO)).

116 s, we show increasing Hedgehog signaling via Smoothened M2 expression rescues some Inpp5e(-/-) ciliop

117 Moreover, they suggest that Gli1 and Smoothened may not be functionally redundant, and direct

118 o the integral membrane proteins Patched and Smoothened, members of the Drosophila Ihog family of adh

119 moothened, through a mechanism distinct from Smoothened modulation by other lipids.

120 Both target the Smoothened molecule and are indicated for locally advanc

121 ontext of all reported resistance-conferring Smoothened mutants and GLI2 overexpression.

122 We previously demonstrated that active Smoothened mutants are subjected to prolonged endoplasmi

123 Upon UPR induction, active Smoothened mutants are targeted by ER-associated degrada

124 window to be evaluated for targeting active Smoothened mutants in disease.

125 egulated Hedgehog signaling driven by active Smoothened mutants is specifically attenuated by ER stre

126 in cases where signaling is driven by active Smoothened mutants that exhibit reduced sensitivity to t

127 re, the effect of oxysterols is abolished in Smoothened mutants that retain activation by cholesterol

128 Acquired Smoothened mutations, including SMO(D477G), confer resis

129 contributions of the Hh signaling transducer Smoothened (MZsmo mutants) and therefore are completely

130 cord phenotype of zebrafish maternal-zygotic smoothened (MZsmo) mutants that completely lack Hh signa

131 bellar development, ASC knockout mice on the Smoothened (ND2:SmoA1) transgenic model of medulloblasto

132 e-resistant acid phosphatase, and cyclin D1, smoothening of leukemic cells' hairy surface, and, event

133 the level of the HH effector and drug target Smoothened or at the level of the GLI transcription fact

134 ddition, we found that polycystin-2, but not smoothened or fibrocystin, requires the biogenesis of ly

135 ened inhibitors occurs by genetic changes of Smoothened or other downstream Hedgehog components.

136 cell maintenance and a basal phenotype (SMO (smoothened), p63, SLUG (snail-2), KER14 (keratin-14) and

137 Here, we report that the Smoothened receptor (Smo) antagonist cyclopamine acts as

138 The Smoothened receptor (SMO) belongs to the Class Frizzled

139 The Smoothened receptor (SMO) mediates signal transduction i

140 Using Shh(Cre:GFP) mice to delete the Smoothened receptor in the Shh pathway, we demonstrate t

141 r-3 (S1P3), the melanocortin-4 receptor, the Smoothened receptor, formyl peptide receptor-2 (FPR2), t

142 nsights regarding cyclopamine binding to the Smoothened receptor.

143 yielded several antagonists of the GPCR-like smoothened receptor.

144 the wild-type and drug-resistant form of the Smoothened receptor.

145 d1 regulates the seven-transmembrane protein Smoothened remains mysterious, partially due to limitati

146 egulate the availability of small lipophilic Smoothened repressors whose identity is unknown.

147 particle irradiation can cause surface ultra-smoothening, self-organized nanoscale pattern formation

148 We report here that Sonic Hedgehog (Shh)-Smoothened signaling downregulates Shisa2, which inhibit

149 oproteins contain lipids required to repress Smoothened signaling in vivo.

150 n on how Wnt/beta-catenin and sonic hedgehog-Smoothened signaling mechanisms control the specificatio

151 ehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is reg

152 Removal of Sufu in both Smoothened (Smo) and Ift88 mutants, respectively, leads

153 primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins

154 ic-membrane-associated Shh signal transducer Smoothened (Smo) and the transcription factor Gli, which

155 ced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1.

156 the results of recent clinical trials using smoothened (SMO) antagonists to inhibit the growth of he

157 The co-receptors Patched (Ptc) and Smoothened (Smo) are expressed by the neighboring skelet

158 signaling proteins such as Patched (Ptc) and Smoothened (Smo) are required for PGC localization to so

159 Although the receptors Patched (Ptch1) and Smoothened (Smo) are required for Shh signaling, a numbe

160 inactivation of the Hedgehog signal mediator Smoothened (Smo) as well as by systemic administration o

161 onformational state of the GPCR-like protein Smoothened (Smo) but how Smo relays the signal to cytopl

162 ts signal transducer and GPCR-family protein Smoothened (Smo) by inducing Smo phosphorylation, but wh

163 s requires activation of the 7TM oncoprotein Smoothened (Smo) by mechanisms that may involve endogeno

164 omotes high-level Hh signaling by regulating Smoothened (Smo) conformation through both kinase-depend

165 bit Shh non-cell autonomously, activation of Smoothened (Smo) drastically increases Hhip internalizat

166 Although inhibitors of membrane protein smoothened (SMO) effectively suppress HH signalling, ear

167 n in vitro, and depletion of the Hh effector Smoothened (Smo) from stromal cells is associated with t

168 C-0449, an inhibitor of Hh pathway component smoothened (Smo) has shown promise in the treatment of v

169 or Patched (PTCH) or activating mutations in Smoothened (SMO) have been reported in basal cell carcin

170 ary Hedgehog (Hh) signalling pathway; Hh and Smoothened (Smo) homologs are absent, but two highly rel

171 Hh-related tumors by specifically activating Smoothened (Smo) in both Hh-producing and -responsive ce

172 otein coupled receptor (GPCR) family protein Smoothened (Smo) in Drosophila, but how PKA activity is

173 xpression of the seven-transmembrane protein Smoothened (Smo) in Drosophila, but the underlying mecha

174 ic gene 1 (Gas1) and its signaling component smoothened (Smo) in enteric neurons.

175 nts result in EvC, we analysed EVC, EVC2 and Smoothened (SMO) in IFT-A deficient cells.

176 Tulp3 acts genetically downstream of Shh and Smoothened (Smo) in neural tube patterning and exhibits

177 ity through activation of the Shh coreceptor Smoothened (Smo) in neurons.

178 -1955) unravel the finding that depletion of Smoothened (Smo) in pancreatic stromal fibroblasts resul

179 e Hedgehog signaling via genetic ablation of Smoothened (Smo) in stromal fibroblasts in a Kras(G12D)

180 ilia by the ligand-triggered accumulation of Smoothened (Smo) in the ciliary membrane.

181 es not affect cilia length or trafficking of smoothened (Smo) in the cilium.

182 Accumulation of the signaling protein Smoothened (Smo) in the membrane of primary cilia is an

183 Pharmacologic inhibition of the Hh effector Smoothened (Smo) increased trabecular bone in vivo and i

184 Smoothened (Smo) inhibition by Patched (Ptch) is central

185 n, a side by side comparison between Gli and Smoothened (Smo) inhibition was conducted in vitro using

186 g, and hyperproliferation was not blocked by smoothened (SMO) inhibition, suggesting a non-canonical

187 thesize that blockade of the Hh pathway with smoothened (Smo) inhibitor can prevent the development o

188 that basal cell carcinomas resistant to the Smoothened (SMO) inhibitor vismodegib frequently harbor

189 ligands and inhibited in the presence of the Smoothened (SMO) inhibitor, cyclopamine.

190 Tumor resistance is an emerging problem for Smoothened (SMO) inhibitor-treated metastatic basal cell

191 Smoothened (SMO) inhibitors are under clinical investiga

192 Smoothened (SMO) inhibitors recently entered clinical tr

193 omas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms.

194 e been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel targeted therapy ag

195 Unlike other Smoothened (Smo) inhibitors, the drug resistance was nei

196 of 60 tested CLL samples responded to all 3 SMOOTHENED (SMO) inhibitors, whereas 40% were completely

197 Smoothened (Smo) is a 7-transmembrane protein essential

198 The seven transmembrane protein Smoothened (Smo) is a critical component of the Hedgehog

199 Smoothened (SMO) is a G-protein-coupled receptor-related

200 The proto-oncogene Smoothened (Smo) is a key transducer of the Shh pathway.

201 Smoothened (Smo) is a member of the Frizzled (FzD) class

202 Smoothened (Smo) is a seven-transmembrane (7-TM) recepto

203 gnaling through the plasma membrane receptor Smoothened (Smo) is an important process for regulating

204 Significantly, we found Smoothened (Smo) is enriched in Arl13b-null cilia regard

205 The seven-transmembrane domain (7TM) protein Smoothened (Smo) is essential for the activation of all

206 Smoothened (Smo) is essential for transduction of the He

207 The Patched1 (Ptch)-mediated inhibition of Smoothened (Smo) is still an open question.

208 nt phosphorylation of the serpentine protein Smoothened (Smo) leads to Ci activation, whereas PKA-dep

209 stitution assays, we demonstrate that dermal Smoothened (Smo) loss of function results in the loss of

210 Smoothened (Smo) mediated Hedgehog (Hh) signaling plays

211 tores sclerotome, whereas Pax1 expression in smoothened (Smo) mutants is not rescued, suggesting that

212 Loss of Hh signaling, in smoothened (smo) mutants, disrupts the expression of som

213 ution, but not lumen opening, is impaired in smoothened (smo) mutants, indicating that fluid-driven l

214 A number of Smoothened (SMO) pathway antagonists are currently under

215 ctivation of the Hedgehog signaling molecule Smoothened (Smo) promoted the clonogenicity of human SCL

216 ps mediate Hh transduction between activated Smoothened (Smo) protein and the negative regulator Supp

217 How Hh-induced activation of transmembrane Smoothened (Smo) proteins reverses Ci/Gli inhibition by

218 and colocalization of Hh, Patched (Ptc) and Smoothened (Smo) proteins tagged with GFP or mCherry and

219 The Smoothened (Smo) receptor is the major transducer of the

220 Activation of the Smoothened (Smo) receptor mediates Hedgehog (Hh) signali

221 The smoothened (SMO) receptor, a key signal transducer in th

222 The transmembrane protein Smoothened (Smo) relays the Hh signal and is an importan

223 The activation of Smoothened (Smo) requires phosphorylation at three clust

224 hog homologs, shh and twhh or Hh co-receptor smoothened (smo) resulted in similar defects in endocard

225 hibitors targeting the Shh pathway component Smoothened (Smo) show great therapeutic promise.

226 rotein-coupled receptor (GPCR)-like molecule Smoothened (Smo) undergoes dynamic intracellular traffic

227 d Notch1 leads to pronounced accumulation of Smoothened (Smo) within primary cilia and elevated level

228 tion of the seven-pass transmembrane protein Smoothened (Smo) within the primary cilium and of the zi

229 otein, lead to modulation of the function of Smoothened (Smo), a 7-pass integral membrane protein, ha

230 oss the membrane by the heptahelical protein Smoothened (Smo), a developmental regulator, oncoprotein

231 ecification utilizing zebrafish mutations in Smoothened (Smo), a G protein-coupled receptor essential

232 t in SMO (c.1234C>T [p.Leu412Phe]), encoding smoothened (SMO), a G-protein-coupled receptor that tran

233 used on developing small molecules targeting Smoothened (Smo), a key signaling effector of the HH pat

234 uires signaling by the transmembrane protein Smoothened (Smo), a member of the G-protein-coupled rece

235 al transduction is the regulated movement of Smoothened (Smo), a seven-transmembrane protein, to the

236 lecule antagonist of the hedgehog coreceptor Smoothened (Smo), abrogated the activation of hedgehog s

237 Here we show that the loss of Smoothened (Smo), an essential component of the Hh pathw

238 Evidence supporting the functionality of Smoothened (SMO), an essential transducer in most pathwa

239 this question, we generated embryos in which smoothened (Smo), an essential transducer of Hedgehog (H

240 during different types of liver injury after Smoothened (SMO), an obligate intermediate in the Hedgeh

241 on of these negative regulators converged on Smoothened (SMO), an oncoprotein that transduces the Hh

242 fluences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh s

243 dgehog (SHH) pathway, SHH, patched (PTCH-1), smoothened (SMO), GLI-1, and GLI-2 and of the NOTCH sign

244 hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medul

245 Shh signaling receptors, Patched (Ptch) and Smoothened (Smo), in the hippocampal neurons of young an

246 minated an essential Hh signaling component, Smoothened (Smo), in the pancreatic epithelium, and asse

247 onic hedgehog (SHH), an activating ligand of smoothened (SMO), is overexpressed in > 70% of pancreati

248 its receptor Patched causes derepression of Smoothened (Smo), resulting in the activation of the Hh

249 Smoothened (Smo), the gene encoding the principal signal

250 relapsed with a D473H resistance mutation in Smoothened (SMO), the molecular target of GDC-0449.

251 activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway

252 Hh pathway in adult bone repair, we deleted Smoothened (Smo), the receptor that transduces all Hh si

253 NF-kappaB pathway in DLBCL tumors, and that smoothened (SMO), the signal transducer subunit of Hh pa

254 hedgehog pathway proteins, such as GLI2 and smoothened (SMO), translocate from the cell into the cil

255 ition of Hh signaling, through inhibition of smoothened (SMO), was an effective strategy to target CP

256 transduced through the transmembrane protein Smoothened (SMO), which localizes to the primary cilium

257 Classical HH signaling is characterized by Smoothened (Smo)-dependent activation of Gli1 and Gli2,

258 Hedgehog (HH) signaling is characterized by Smoothened (Smo)-dependent activation of the transcripti

259 8(+) MM cells express Hh genes and confirmed Smoothened (Smo)-dependent Hh signaling in MM using a no

260 constitutive Gli activity is activated in a Smoothened (Smo)-independent fashion, consistent with it

261 Arhgap36 acts in a Smoothened (Smo)-independent manner to inhibit Gli repre

262 Gli2 activation is able to fully rescue the Smoothened (Smo)-null intestinal phenotype, suggesting t

263 patched 1 (Ptch1) and the pathway activator smoothened (Smo).

264 of the downstream G-protein-coupled receptor Smoothened (SMO).

265 Ptc) elicits intracellular signaling through Smoothened (Smo).

266 eveloped, most notably through inhibition of Smoothened (SMO).

267 ltipass membrane proteins, patched (Ptc) and smoothened (Smo).

268 commonly through acquisition of mutations in Smoothened (Smo).

269 roles in C. elegans that are independent of Smoothened (Smo).

270 otype induced by a dominant negative form of Smoothened (Smo).

271 ding GDC-0449, a small molecule inhibitor of Smoothened (SMO).

272 LDE225), which block the HH pathway effector Smoothened (SMO).

273 receptor complex relieves Ptc inhibition on Smoothened (Smo).

274 gib and sonidegib are targeted inhibitors of Smoothened (SMO).

275 otein coupled receptor (GPCR)-family protein Smoothened (Smo).

276 Somatostatin Receptor 3 (SSTR3, a GPCR) and Smoothened (Smo, a Hedgehog signal transducer) in the ci

277 ) signaling, because it was abolished by the smoothened (SMO; the transducer of Hh signaling) inhibit

278 Mutations in SMO (encoding Smoothened, SMO) are common in ameloblastomas of the max

279 iated by Hh ligands results in activation of Smoothened (SMOH) and culminates in the activation of th

280 inducing expression of constitutively active Smoothened (SmoM2) or Gli2 (DeltaNGli2) in the adipocyte

281 ulation, we expressed an oncogenic allele of Smoothened (SmoM2) to cell autonomously activate Hh sign

282 phenocopy transgenic expression of activated smoothened (SmoM2).

283 or cells lack expression of the Hh receptor, Smoothened, suggesting an Hh-independent mechanism of Gl

284 gh inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistan

285 Smoothened suppression in primary HSCs using a Hh antago

286 ing RNA tertiary folding where they may help smoothen the folding landscape by allowing folding to pr

287 2, and this regulation occurs independent of Smoothened, the central transducer of the Hedgehog canon

288 ormally regulate canonical Hh-signalling via smoothened, the mes mutation causes, among other non-let

289 nents of the hedgehog pathway independent of Smoothened, the obligatory signal transducer of the path

290 tion of the essential transduction component Smoothened, through a mechanism distinct from Smoothened

291 gating the translocation of the key effector Smoothened to primary cilia and its downstream signaling

292 nt cholesterol binding impair the ability of Smoothened to transmit native Hh signals.

293 G protein-coupled receptors (GPCRs), but not Smoothened, to cilia.

294 with or without inhibitors of WNT (DKK1) or Smoothened (vismodegib) and then cocultured with immorta

295 Smoothened was required for TGF-beta1-induced myofibrobl

296 hich the Hedgehog signaling pathway effector Smoothened was specifically invalidated in endothelial c

297 is the ciliary trafficking and activation of Smoothened, which by increasing Gpr161-beta-arrestin bin

298 Shh signaling have focused on inhibitors of Smoothened, which target the canonical Shh signaling pat

299 Hh and is replaced by the signal transducer Smoothened within an hour of Hh stimulation.

300 accumulation and activation of the effector Smoothened within cilia and concomitant disappearance of