ライフサイエンスコーパス: smoothen

1 ain and TMD stabilizes the inactive state of Smoothened.

2 identify EHD1 as a direct binding partner of Smoothened.

3 that cholesterol itself binds and activates Smoothened.

4 dependent of the Hedgehog pathway transducer Smoothened.

5 erol and the mechanism by which it regulates Smoothened.

6 ous class A G protein-coupled receptors, and Smoothened.

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

8 gradation of the Hedgehog pathway transducer Smoothened.

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

10 zed but is thought to be mainly dependent on Smoothened.

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

12 valleys of the surface growth front leads to smoothening.

13 ng asperities results in progressive surface smoothening.

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

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

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

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

18 essential for canonical Hh signaling through smoothened, a transmembrane protein targeted by small-mo

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

20 mozygous Megf8 and Mgrn1 mutations increased Smoothened abundance and elevated sensitivity to Hedgeho

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

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

23 distinct pools of cholesterol, we find that Smoothened activation and Hedgehog signaling are driven

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

25 holesterylated SHH, and Patched1 antagonizes Smoothened activation by cholesterol.

26 n the bilayer is sufficient for constitutive Smoothened activation.

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

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

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

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

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

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

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

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

35 cer, Smoothened, and an impaired response to Smoothened agonist, SAG.

36 Interestingly, Smoothened agonist-SAG rescued OAF cell proliferation an

37 T and Smoothened(-/-) fibroblasts as well as Smoothened agonist-stimulated cells.

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

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

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

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

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

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

44 Wild-type Smoothened and physiological Hedgehog patterning were no

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

46 ritical incidence angle, which separates the smoothening and roughening regimes.

47 ransport defect for the Hedgehog transducer, Smoothened, and an impaired response to Smoothened agoni

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

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

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

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

52 ells, transduced across the cell membrane by smoothened, and transmitted to the nucleus by GLI protei

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

54 Smoothened antagonists directly target the genetic basis

55 es a possible explanation for the failure of Smoothened antagonists in combating Hedgehog-dependent b

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

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

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

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

60 genetic lesions rendering them resistant to Smoothened antagonists.

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

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

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

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

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

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

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

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

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

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

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

72 ified an elaborate signaling network of both Smoothened-dependent and -independent pathways that medi

73 Moreover, several Smoothened-dependent effects (e.g. neurite projection) d

74 esting biological importance of noncanonical Smoothened-dependent pathways.

75 tive therapies as compared with conventional Smoothened-directed therapies.

76 and Ttc21b and embryos expressing activated Smoothened, display apical constriction defects in later

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

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

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

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

81 kinome in Hedgehog-challenged murine WT and Smoothened(-/-) fibroblasts as well as Smoothened agonis

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

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

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

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

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

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

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

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

90 from producing cells, and directly activates Smoothened in responding cells.

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

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

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

94 1 protein co-localizes with the SHH receptor Smoothened in the primary cilia upon ligand stimulation.

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

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

97 letion of the obligate Hedgehog co-receptor, Smoothened, in Sox9-expressing cells prior to injury res

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

99 nonical Hh signaling, GLI1 is activated in a Smoothened-independent manner.

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

101 pendent cancer, suggesting that noncanonical Smoothened-independent pathways also are clinically rele

102 The contribution of noncanonical Smoothened-independent signaling to the overall effects

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

104 The observation that Patched-dependent, Smoothened-independent, noncanonical Hedgehog signaling

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

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

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

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

109 f IPF fibroblasts was partially resistant to Smoothened inhibition.

110 Importantly, smoothened inhibitor treatment ameliorated metachondroma

111 The SMOOTHENED inhibitor vismodegib is FDA approved for adva

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

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

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

115 Strikingly, Smoothened inhibitor-resistant BCCs have an increased mu

116 agonists in combating Hedgehog-dependent but Smoothened inhibitor-resistant cancer.

117 recapitulated in control mice treated with a Smoothened inhibitor.

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

119 Despite naive tumor responsiveness to Smoothened inhibitors (Smo(i)), resistance in advanced t

120 However, Smoothened inhibitors have yielded only partial success

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

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

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

124 is and the emerging clinical experience with smoothened inhibitors.

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

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

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

128 edgehog signal across the plasma membrane by Smoothened is triggered by its interaction with choleste

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

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

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

132 tant cells, similar to our 3D results on the Smoothened-measured ciliary surface.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

152 The Smoothened receptor (SMO) mediates signal transduction i

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

154 inding to Patched followed by alleviation of Smoothened receptor inhibition, leading to activation of

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

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

157 nsights regarding cyclopamine binding to the Smoothened receptor.

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

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

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

161 In contrast, Patched1 repression of Smoothened requires the opposing K(+) gradient.

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

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

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

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

166 n releases its inhibition of the oncoprotein Smoothened (SMO) after binding the HH ligand, triggering

167 These factors include smoothened (SMO) and patched, which constitute the core

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

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

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

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

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

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

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

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

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

177 cilia blocks the exit of GPR161, SSTR3, and Smoothened (SMO) from cilia.

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

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

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

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

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

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

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

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

186 -1955) unravel the finding that depletion of Smoothened (Smo) in pancreatic stromal fibroblasts resul

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

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

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

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

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

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

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

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

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

196 Gli signaling, but can develop mechanisms of Smoothened (SMO) inhibitor resistance.

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

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

199 Smoothened (SMO) inhibitors are under clinical investiga

200 However, Smoothened (SMO) inhibitors have failed to show clinical

201 Smoothened (SMO) inhibitors recently entered clinical tr

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

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

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

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

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

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

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

209 Smoothened (SMO) is a GPCR that mediates hedgehog signal

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

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

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

213 At the same time, the transmembrane protein Smoothened (SMO) is released of its inhibition by PTCH1

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

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

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

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

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

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

220 toma and Hh pathway inhibitors targeting the Smoothened (SMO) protein are in clinical use.

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

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

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

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

225 toma mice with constitutive actvation of the Smoothened (Smo) receptor using a PerkinElmer G4 PET-X-R

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

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

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

229 ns of the BBSome with membranes and the GPCR Smoothened (SMO) reveals that SMO, and likely also other

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

231 vation of the seven-transmembrane transducer Smoothened (SMO) via a mechanism that is poorly understo

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

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

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

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

236 The oncoprotein Smoothened (SMO), a G-protein-coupled receptor (GPCR) of

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

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

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

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

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

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

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

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

245 tors target the critical signaling component Smoothened (SMO), but preclinical research has identifie

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

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

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

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

250 rs steady-state levels of ATP and stabilizes Smoothened (Smo), the 7-pass transmembrane protein that

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

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

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 that CBs reduced Shh signaling by inhibiting Smoothened (Smo), while Shh mRNA or a CB1 receptor antag

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

264 vents ciliary accumulation and activation of smoothened (Smo).

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

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

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

268 develops chemoresistance due to mutations in smoothened (SMO).

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

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

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

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

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

274 receptors consists of 10 FZD paralogues and Smoothened (SMO).

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

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

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

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 phenocopy transgenic expression of activated smoothened (SmoM2).

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

283 Smoothened suppression in primary HSCs using a Hh antago

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

285 e atoms away from the dendrite tips, thereby smoothening the dendritic surface.

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

287 ely depended on the presence of cilia and on smoothened, the obligate transducer of Shh signaling, in

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

289 transcriptional regulator YAP1 downstream of Smoothened, the positive transducer of SHH signaling.

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

294 Smoothened was required for TGF-beta1-induced myofibrobl

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

296 ural and functional analysis of Frizzled and Smoothened, we aim to summarize what we know about the m

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 ciliary transmembrane proteins, specifically Smoothened, with single fluorescent labels in fixed cell

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