ライフサイエンスコーパス: FGFR4

1 FGF19 uniquely binds to FGF receptor 4 (FGFR4).

2 cardiac myocytes via FGF receptor isoform 4 (FGFR4).

3 iation is modulated by 2 genetic variants in FGFR4.

4 able to activate FGFRs 1c, 2c and 3c but not FGFR4.

5 -regulated in human and mouse hepatomas than FGFR4.

6 nes expressing the empty vector or wild-type FGFR4.

7 receptor 3 (FGFR3) but not FGFR1, FGFR2, or FGFR4.

8 ctively blocks the interaction of FGF19 with FGFR4.

9 increased the interactions between FGF19 and FGFR4.

10 ignancies involving interaction of FGF19 and FGFR4.

11 ever, only FGF19 signals efficiently through FGFR4.

12 that is also present in FGFR1c, FGFR3c, and FGFR4.

13 + cells are quite rare, as is expression of FGFR4.

14 is unique in binding solely to one receptor, FGFR4.

15 lobal deletion or constitutive activation of FGFR4.

16 t activity in PC lines expressing endogenous FGFR4.

17 endocrine FGFs and FGFR1/Klb, or FGF19 with FGFR4.

18 lice forms of FGFR1 to -3 as well as towards FGFR4.

19 mutation was generated in FGFR1, FGFR3, and FGFR4.

20 crossing into the brain, possibly acting via FGFR4.

21 ce the expression of RGS14 itself, MXD3, and FGFR4.

22 of FGF23 on aortic relaxation do not require FGFR4.

23 s HCC development in a process that requires FGFR4.

24 embers of the FGF family, including Fgf6 and Fgfr4.

25 rgeting Fibroblast Growth Factor Receptor 4 (FGFR4), a highly expressed surface tyrosine receptor in

26 FGF19 antibody and siRNA specific to FGFR4 abrogated GW4064 inhibition of CYP7A1.

27 38-42 of FGF19 are sufficient to confer both FGFR4 activation and increased hepatocyte proliferation

28 n were abolished, and betaKlotho-independent FGFR4 activation was preserved; therefore, FGF19dCTD is

29 FGFR4 activity in hepatocytes that normally serves to pr

30 ults demonstrate that mutationally activated FGFR4 acts as an oncogene, and these are what we believe

31 The results show that FGFR4 acts by promotion of processes that restore hepato

32 Our findings highlight the importance of the FGFR4 allele in pNET progression and identify a predicti

33 nation for the unusual affinity of FGF19 for FGFR4 alone.

34 of renal disease, however, whether FGF23 and FGFR4 also contribute to CKD remains unknown.

35 Ablation of FGFR4 also failed to correct hypophosphatemia in Hyp mic

36 f liver pathophysiology that acts through an FGFR4-AMPK-Caspase 6 signal pathway, shedding light on s

37 The objective was to determine the role of FGFR4, an isotype that has been proposed to mediate an i

38 g the model predicted synergy of cotargeting FGFR4 and AKT or specific ErbB kinases, which was subseq

39 nerated a mouse model with dual deletions of FGFR4 and alpha-klotho, and we induced CKD in mice with

40 Factors required for FGF19 signaling (i.e., FGFR4 and betaKlotho) are expressed in mucosal epithelia

41 iple for a CAR T-cell therapy targeting both FGFR4 and CD276 in RMS.

42 Bicistronic CARs (BiCisCAR) targeting both FGFR4 and CD276, containing two distinct co-stimulatory

43 lesterol 7alpha-hydroxylase transcription by FGFR4 and cholate.

44 h low FGF19 expression through activation of FGFR4 and downstream signaling cascades.

45 s-regulatory elements at promoter regions of Fgfr4 and Hes1, and regulates their expression.

46 also provide the first direct evidence that FGFR4 and IGF1R are the targets for PAX3-FKHR.

47 parin specifically mediated FGF23 binding to FGFR4 and increased FGF23 stimulatory effects on hypertr

48 there is a synergistic effect of cotargeting FGFR4 and MEK but not AKT.

49 ax3 in head ectoderm is sufficient to induce FGFR4 and Ngn2 expression, but neurons do not differenti

50 ls for expression of the opV placode markers FGFR4 and Ngn2, maintenance of the preplacodal marker Ey

51 xperimental validation; however, cotargeting FGFR4 and PI3K was not synergistic.

52 naling in hepatocytes that primarily express FGFR4 and reduces transcription of CYP7A1 that encodes t

53 is not capable of inducing phosphaturia via FGFR4 and that FGFR4 does not promote or mitigate renal

54 ate dorsoanterior neural development through fgfr4 and ventx2.1.

55 e of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM).

56 studies using TCGA data (e.g., SYNE1, KLF6, FGFR4, and EPHB4).

57 into C2C12 myotubes showed Tead2 to activate Fgfr4, and mutation of the M-CAT motif in the Fgfr4 prom

58 hate transporter, alphaKlotho, FGFR1, FGFR3, FGFR4, and the PTH receptor.

59 ociated with inhibition of FGFR1, FGFR2, and FGFR4, and to be agnostic for the FGFR3 gatekeeper mutat

60 overexpressing constitutively active hepatic FGFR4--and FGFR4(-/-) with constitutively active hepatic

61 The results described herein suggest that FGFR4 antagonists alone, or in combination with other ag

62 eatment of diet-induce obese (DIO) mice with FGFR4 antisense oligonucleotides (ASO) specifically redu

63 Although Fgfr3 and Fgfr4 are expressed in the mesenchyme and epithelium, in

64 ced in myocardium, while receptors fgfr2 and fgfr4 are induced in adjacent epicardial-derived cells.

65 ates that unique sequences in both FGF19 and FGFR4 are key to the formation of the complex.

66 We show that aging mice lacking FGFR4 are protected from LVH.

67 Cas9 approach, we demonstrate that fgfr3 and fgfr4 are required for vertebrate astrocyte morphogenesi

68 F19 and its cognate receptor FGF receptor 4 (FGFR4) are coexpressed in primary human liver, lung and

69 as no correlation between the presence of an FGFR4(arg) allele and CRC or polyp risk in 3,471 partici

70 erns to overexpress either the FGFR4(gly) or FGFR4(arg) alleles.

71 he stronger inducer of tumor growth, whereas FGFR4(arg) was the stronger inducer of migration.

72 mportant implication of our findings is that FGFR4(arg)-carriers are at a higher risk for more aggres

73 However, among 182 patients with CRC, FGFR4(arg)-carriers had a fivefold higher risk of tumors

74 streptozotocin-induced diabetes, implicating FGFR4 as a primary target of insulin regulation.

75 Finally, we propose FGFR4 as a valuable marker for the stratification of PDA

76 UMAP spatial profiling were used to identify FGFR4 as an HNF1A target gene upregulated in metastatic

77 In addition, combination treatment with FGFR4 ASO and rimonabant showed additive reduction in BW

78 FGFR4 ASO treatment increased basal metabolic rate durin

79 tudies indicated that anti-obesity effect of FGFR4 ASO was mediated at least in part through an induc

80 poorly conserved cysteine residue within the FGFR4 ATP-binding site at position 552, two positions be

81 Specific blockade of FGFR4 attenuates established LVH in the 5/6 nephrectomy

82 onds with an increased dependency upon FGF19/FGFR4 autocrine signaling in HNSCC, revealing a therapeu

83 FGF19/FGFR4 autocrine signaling is one of the main targets for

84 d to mediate an ileal FGF15/19 to hepatocyte FGFR4 axis in cholesterol homeostasis, in metabolic home

85 eration and metabolism via the activation of Fgfr4/b-klotho (Klb).

86 that FGF19 acts through the receptor complex FGFR4-beta-Klotho (KLB) to regulate bile acid metabolism

87 FGF19 signaling through the FGFR4/beta-klotho receptor complex has been shown to be

88 ism promoting T2D-associated HFpEF such that FGFR4 blockade might serve as a cardio-protective therap

89 ll-free complexes of heparin and recombinant FGFR4 bound FGF-1 and FGF-2 equally.

90 filling; FGF19 binds only to FGF receptor 4 (FGFR4), but its liver-specific activity cannot be explai

91 ion of the fibroblast growth factor receptor FGFR4 by FGF19 drives hepatocellular carcinoma (HCC), a

92 co-stimulatory and targeting properties of a FGFR4 CAR.

93 grown in vitro, FGF23-mediated activation of FGFR4 caused mitochondrial pathology, characterized by i

94 echanistically, FGF23-mediated activation of FGFR4 causes mitochondrial dysfunction, suggesting that

95 In conclusion, we identified IGF2, FGFR4, CD200, and CD276 as potential therapeutic targets

96 reted growth factor that signals through the FGFR4 cell-surface receptor tyrosine kinase.

97 d ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib.

98 n ingestion of food and binds the betaKlotho-FGFR4 complex in hepatocytes to promote metabolic respon

99 both FGF19 and FGF21 bind to the betaKlotho-FGFR4 complex; however, only FGF19 signals efficiently t

100 that the kinase domains of FGFR1, FGFR3, and FGFR4 containing the activation loop mutation, when targ

101 These studies define KLB as a novel FGFR4 coreceptor required for FGF19 liver specific funct

102 Therefore, FGFR4 could be a potential novel target and antisense re

103 These findings highlight that FGF19/FGFR4 cross-talk with beta-catenin and that pathway inte

104 Surprisingly, the FGFR4 deficiency alleviated high-fat diet-induced fatty

105 Here, we show that FGFR4 deficiency in mice leads to improvement in glucose

106 of serum alanine aminotransferase similar to FGFR4 deficiency, but no effect on overall hepatolobular

107 ure resulted in severe fibrosis in livers of FGFR4-deficient mice compared to normal mice.

108 Following acute CCl(4) exposure, the FGFR4-deficient mice exhibited accelerated liver injury,

109 protein levels indicated an 8-hour delay in FGFR4-deficient mice in the down-regulation of cytochrom

110 FGFR4-deficient mice on a normal diet exhibited features

111 Mechanism of action studies in FGFR4-deficient mice suggest that the effects are mediat

112 ion of FGFR4, specifically in hepatocytes of FGFR4-deficient mice, decreased plasma lipid levels and

113 both acute and chronic exposure to CCl(4) in FGFR4-deficient mice.

114 A model for the complex of FGF19 with FGFR4 demonstrates that unique sequences in both FGF19 a

115 h constitutive activation of FGF receptor 4 (FGFR4)-dependent ERK/AKT-p70S6K-S6 signaling activation

116 unique FGF19 molecule specifically activated FGFR4-dependent signaling in liver and suppressed CYP7A1

117 c background, the increased proliferation of FGFR4-depleted PDAC cells correlates with hyperactivatio

118 nally, we demonstrate that FGFR1, FGFR3, and FGFR4 derivatives can stimulate PI-3 kinase activity.

119 supports the unique intersection of KLB and FGFR4 distribution in liver.

120 of inducing phosphaturia via FGFR4 and that FGFR4 does not promote or mitigate renal injury in anima

121 Notably, suppression of FGFR4 dramatically diminishes glutathione synthesis and

122 occurred in certain cell types, including an FGFR4-driven hepatocellular carcinoma cell line, in whic

123 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC ce

124 In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI trea

125 Conclusion: The hepatic FGF19/FGFR4/Erk1/2 pathway may inhibit CYP7A1 independent of S

126 sults established that both allelic forms of FGFR4 exert an oncogenic impact and may serve equally we

127 Here we show that livers of mice lacking FGFR4 exhibited normal morphology and regenerated normal

128 aggressive basal-like/squamous PDAC, reduced FGFR4 expression aligns with hypermethylation of the gen

129 el target and antisense reduction of hepatic FGFR4 expression could be an efficacious therapy as an a

130 , including an epigenetic mechanism for high FGFR4 expression in breast cancer.

131 ude that HNF1alpha is a major determinant of FGFR4 expression in PC.

132 Higher FGFR4 expression in RMS tumors was associated with advan

133 nable to activate signaling in adipose where FGFR4 expression is very low.

134 FGFR4 expression localized only in the medial habenula a

135 nucleotides (ASO) specifically reduced liver FGFR4 expression that not only resulted in decrease in b

136 ed with FGFR1 expression being lost, whereas FGFR4 expression was expanded beyond its normal expressi

137 f15 uses distinct mechanisms to downregulate Fgfr4 expression, namely retention of a single intron wi

138 res, notably a high immune response and high FGFR4 expression.

139 F15 level resulted from reduction of hepatic FGFR4 expression.

140 xpression of various markers including Pax3, FGFR4, Eya2, and the neuronal differentiation markers Is

141 Here we show that in Fgfr3;Fgfr4 (Fgfr3;4) global mutant mice, alveolar simplificat

142 equally well to complexes of both FGFR1 and FGFR4 formed with endothelial cell-derived HSPG, but the

143 Fibroblast growth factor receptor 4 (FGFR4), Frizzled 9 (Fz9), and SRY box-containing gene 2

144 inhibition of FGF19-dependent activation of FGFR4, FRS2, ERK and beta-catenin.

145 BON1 cells and transfected them with either FGFR4-G388 or FGFR4-R388 to determine the mechanism of a

146 Unlike FGFR4-G388, FGFR4-R388 BON1 tumors exhibited diminished

147 examined the chromatin structure around the FGFR4 gene in a panel of expressing and non-expressing P

148 To evaluate this, we developed 2 FGFR4 genomic signatures using a patient-derived xenogra

149 We established the FGFR4 genotype of 71 patients with pNETs and correlated

150 xpression patterns to overexpress either the FGFR4(gly) or FGFR4(arg) alleles.

151 importance for both polymorphic alleles, but FGFR4(gly) was the stronger inducer of tumor growth, whe

152 Fgfr4 has been shown to be important for appropriate mus

153 The deletion of FGFR4 has no effect on the proliferative response of hep

154 Downregulation of FGFR4 in classical cell lines invariably leads to the en

155 fically assess the impact of the polymorphic FGFR4 in colorectal cancer (CRC), we engineered CRC cell

156 The structures of FGFR4 in complex with the type I inhibitor Dovitinib and

157 we report the identification of mutations in FGFR4 in human RMS tumors that lead to its activation an

158 We also show that expression of FGFR4 in liver was decreased by fasting, increased by in

159 st that pericellular matrix-controlled liver FGFR4 in particular may ensure adequate cholesterol for

160 pport the potential therapeutic targeting of FGFR4 in RMS.

161 but FGF19 was able to interact directly with FGFR4 in the absence of betaKlotho in a heparin-dependen

162 e, we aimed to clarify the role of FGFR1 and FGFR4 in the definition of aggressive PDAC phenotypes.

163 osine phosphorylation of the FGF receptor 4 (FGFR4) in hepatocytes.

164 FGFR type 4 (FGFR4) in liver parenchymal cells binds only FGF-1, wher

165 tion of fibroblast growth factor receptor 4 (FGFR4) in peripheral tissues.

166 role of fibroblast growth factor receptor 4 (FGFR4) in regulating bile acid synthesis has been well d

167 s the first demonstration that activation of FGFR4, in addition to FGFR1 and FGFR3, can induce cellul

168 sent four structures of the kinase domain of FGFR4, in its apo-form and in complex with different typ

169 Consortium (METABRIC) breast cancer cohort, FGFR4-induced and FGFR4-repressed signatures each predic

170 multivariate analysis demonstrated that the FGFR4-induced signature also predicted site-specific met

171 Additionally, the FGFR4-induced signature was an independent prognostic fa

172 ors with paired metastases revealed that the FGFR4-induced signature was significantly higher in lumi

173 Because the ablation of neither FGFR3 nor FGFR4 inhibited the renal effects of excess FGF23, the k

174 were utilized to demonstrate the efficacy of FGFR4 inhibiting agents at reducing HNF1A-driven metasta

175 RNAi and two FGFR4 inhibiting modalities (H3B-6527 and U3-1784) were

176 hepatocellular carcinomas, making selective FGFR4 inhibition an attractive treatment opportunity.

177 Taken together our results suggest FGFR4 inhibition as a safe alternative strategy to targe

178 FGFR4 inhibition enhances susceptibility to anti-HER2 th

179 activation, Taqman analyses show that FGF19/FGFR4 inhibition reduced beta-catenin target gene (cycli

180 of oxidative cell death, is triggered after FGFR4 inhibition.

181 , disrupting FGF19 via gene silencing or the FGFR4 inhibitor BLU9931 recapitulates most phenotypes ob

182 Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/

183 injection of BLU9931, a relatively selective FGFR4 inhibitor, also decreased the responses in HP rats

184 erated H3B-6527, a highly selective covalent FGFR4 inhibitor, through structure-guided drug design.

185 erived xenograft (PDX) model treated with an FGFR4 inhibitor, which inhibited PDX growth in vivo.

186 may assist in the design and development of FGFR4 inhibitors.

187 ponse to FGF19 treatment and increased FGF19-FGFR4 interactions in vitro, similar to the effects of b

188 ce that KLB is required for FGF19 binding to FGFR4, intracellular signaling, and downstream modulatio

189 Coordinate expression of betaklotho and FGFR4 is a property of mature hepatocytes.

190 eve high potency and isoform selectivity for FGFR4 is covalently targeting a rare cysteine (C552) in

191 FGF signaling through receptors Fgfr3 and Fgfr4 is crucial for alveologenesis, but the mechanisms

192 inition of liver from foregut endoderm where FGFR4 is expressed and stimulation of hepatocyte DNA syn

193 r FGF receptor (FGFR) tyrosine kinases, only FGFR4 is expressed in mature hepatocytes.

194 GF) receptor genes expressed in adult liver, FGFR4 is expressed specifically in mature hepatocytes.

195 The receptor tyrosine kinase FGFR4 is highly expressed in RMS tissue, suggesting a ro

196 FGFR4 is involved in myogenesis and muscle regeneration.

197 the endoderm implies that signaling through FGFR4 is involved in specifying lung versus liver.

198 comes highly abnormal at the time point when Fgfr4 is normally expressed.

199 In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor eff

200 lated transmembrane tyrosine kinase receptor FGFR4 is the major FGFR isotype in mature hepatocytes.

201 FGFR4 is the major hepatic FGF receptor isoform and is r

202 These data suggest that activation of FGFR4 is the mechanism whereby FGF19 can increase hepato

203 In summary, neither FGFR3 nor FGFR4 is the principal mediator of FGF23 effects in the

204 We have shown that FGFR4 is widely distributed in mouse, whereas KLB distri

205 in of the fibroblast growth factor receptor (FGFR4) is associated with increased risk, staging, and m

206 Fibroblast growth factor receptor 4 (FGFR4) is expressed in 50-70% of pancreatic carcinomas (

207 Fibroblast growth factor receptor 4 (FGFR4) is thought to be a driver in several cancer types

208 cturally characterized, the structure of the FGFR4 kinase domain has not yet been reported.

209 The two apo-FGFR4 kinase domain structures show an activation segmen

210 ther endocrine FGF19 or cellular FGF1 of the FGFR4 kinase in a complex with betaklotho restricts cell

211 The FGF19-FGFR4-KLB pathway links regulation of BA synthesis to co

212 vanced-stage cancer and poor survival, while FGFR4 knockdown in a human RMS cell line reduced tumor g

213 number of ki67-positive nuclei is reduced in FGFR4 knockdown tumor xenograft tissues.

214 FGFR4 knockdown using inducible short hairpin RNA signif

215 hese cases, we developed the hypothesis that FGFR4 likely participates in this subtype switching.

216 In sum, we show that endogenous levels of FGFR4 limit the malignant phenotype of PDAC cells.

217 of-function mutations in lung cancer, namely FGFR4, MAP3K9, and PAK5.

218 Mutations affecting the kinase domain of FGFR4 may cause cancer, for example, breast cancer or rh

219 The mechanism underlying the FGFR4-mediated hepatoma suppression has not been address

220 ate that FGF signalling, via FGF receptor 4 (Fgfr4), mediates a signal-transduction pathway between W

221 However, the FGFR4 (-/-) mice exhibited depleted gallbladders, an ele

222 ent, cholesterol-induced hepatomegaly in the FGFR4 (-/-) mice suggested that activation of receptor i

223 FGFR4(-/-) mice-mice overexpressing constitutively activ

224 sting that early pharmacologic inhibition of FGFR4 might serve as novel therapeutic intervention to p

225 RMS cell lines expressing the K535 and E550 FGFR4 mutants were substantially more susceptible to apo

226 inically actionable genes including gains of FGFR4 (n = 6 [30%]), FLT1 (n = 4 [20%]), AURKA (n = 2 [1

227 t exogenous expression of HNF1 factors in an FGFR4 non-expressing line led to an induction of enhance

228 t staged induction of muscle regeneration in Fgfr4 null mice becomes highly abnormal at the time poin

229 cle development in chick limb buds; however, Fgfr4 null mice show no phenotype.

230 Genetic deletion of FGFR4 or betaklotho in mice disrupts hepatic cholesterol

231 ll four tyrosine kinase FGF receptors (FGFR1-FGFR4), other members demonstrate a higher degree of sel

232 The betaklotho-FGFR4 partnership caused a depression of activated AKT a

233 Thus the same betaklotho-heparan sulfate-FGFR4 partnership that mediates endocrine control of hep

234 Our data suggest a novel MyoD-Tead2-Fgfr4 pathway important for effective muscle regeneratio

235 suggest that selectively targeting the FGF19-FGFR4 pathway may offer a tractable approach to improve

236 chanistically, m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-cateni

237 To determine whether FGFR4 plays a broader role in liver-specific metabolic f

238 FGFR4 plays essential roles in systemic lipid and glucos

239 metastasis, suggesting treatment options for FGFR4-positive patients, whose high expression is not ca

240 ed during the optimization are improving the FGFR4 potency, metabolic stability, and solubility leadi

241 gfr4, and mutation of the M-CAT motif in the Fgfr4 promoter abolished these effects.

242 The Fgfr4 promoter region contained a Tead protein binding s

243 Co-transfection of Tead2 and Fgfr4 promoter reporter constructs into C2C12 myotubes s

244 These results show that hepatocyte FGFR4 protects against acute and chronic insult to the l

245 Unlike FGFR4-G388, FGFR4-R388 BON1 tumors exhibited diminished responsivene

246 FGFR4-R388 is associated with more aggressive clinical b

247 thotopic mouse xenograft model, we show that FGFR4-R388 promotes tumor progression by increasing intr

248 d transfected them with either FGFR4-G388 or FGFR4-R388 to determine the mechanism of action and to e

249 n in response to everolimus in patients with FGFR4-R388.

250 Chimeric FGFR1c/FGFR4 receptors were constructed to identify domains tha

251 These data identify a link between FGFR4-regulated genes and metastasis, suggesting treatme

252 uction during regeneration commensurate with Fgfr4 regulation.

253 RIC) breast cancer cohort, FGFR4-induced and FGFR4-repressed signatures each predicted overall surviv

254 GFR4(-/-) with constitutively active hepatic FGFR4 restored in the liver were subjected to a normal a

255 from liver cells in cell-free complexes with FGFR4 restored the specificity for FGF-1 and supported t

256 SNPs of fibroblast growth factor receptor 4 (FGFR4) revealed that rs1966265 (Val10Ile) and rs351855 (

257 2E1 rs6413432, ERCC1 rs11615, ERCC2 rs13181, FGFR4 rs351855, HYKK rs931794, MIR146A rs2910164, MIR196

258 the Hippo kinases Mst1/2, thereby switching FGFR4's role from pro-oncogenic to anti-tumor signaling.

259 gies for targeting this cysteine to identify FGFR4 selective inhibitor starting points are summarized

260 g the hemodialysis procedure, regulate FGF23/FGFR4 signaling and effects in cardiac myocytes.

261 velop a comprehensive computational model of FGFR4 signaling and to provide network-level insights in

262 quencing demonstrated that the inhibition of FGFR4 signaling caused molecular switching.

263 Ablation of pathologic FGF23-FGFR4 signaling did not protect mice on an increased pho

264 However, inhibiting FGF19/FGFR4 signaling in HCC patients is associated with toxic

265 r, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepa

266 Further, FGF19 activated FGFR4 signaling in the presence or absence of betaKlotho

267 together, our data highlight a role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling

268 of concentric hypertrophy by elevated FGF21-FGFR4 signaling may constitute a novel mechanism promoti

269 rmacological interference with cardiac FGF23/FGFR4 signaling might protect from CKD- and age-related

270 in hepatocytes may activate the liver FGF19/FGFR4 signaling pathway to inhibit bile acid synthesis a

271 Oncogenic FGFR4 signaling represents a potential therapeutic targe

272 Further, knockdown and inhibition of FGFR4 significantly decreases HNF1A-mediated cell migrat

273 However, resistance to FGFR4 single-agent therapy remains a major challenge, em

274 on was preserved; therefore, FGF19dCTD is an FGFR4-specific activator.

275 i-tumor activities compared to the optimized FGFR4-specific CAR and the other BiCisCAR with the same

276 Restoration of FGFR4, specifically in hepatocytes of FGFR4-deficient mi

277 n of Wnt target GLUL, pharmacological target FGFR4, stemness markers EPCAM and KRT19 and immune check

278 d hepatocellular carcinomas, indicating that FGFR4 suppresses hepatoma proliferation.

279 uncovered potent AKT reactivation following FGFR4 targeting in triple-negative breast cancer cells.

280 (FGFRs) 1c, 2c, and 3c, only FGF19 activates FGFR4, the predominant receptor in the liver.

281 otho not only interacts with heparan sulfate-FGFR4 to form a complex with high affinity for endocrine

282 erohepatic FGF15 stimulates hepatic receptor FGFR4 to recruit and phosphorylate NF2, which relieves t

283 in the intestine, which acts through hepatic FGFR4 to suppress cholesterol-7alpha hydroxylase (CYP7A1

284 af15 is depleted, and reduction in the total fgfr4 transcript when zygotic Taf15 alone is depleted.

285 Here we determine the sites of FGFR4 transcriptional initiation which show a pattern ch

286 nine (R) for glycine (G) in codon 388 of the FGFR4 transmembrane domain.

287 Moreover, 6 FGFR4 tyrosine kinase domain mutations were found among

288 Recently, we showed that mice in which FGFR4 was ablated from the germline exhibited elevated c

289 Genetic variation in FGFR4 was associated with AC t((1/2)) in response to CDC

290 found that posterior expression of FGFR1 and FGFR4 was dependent on the expression of RARalpha2.

291 ever, in contrast to FGFR1, when recombinant FGFR4 was expressed back in epithelial cells by transfec

292 aluation of clinical specimens revealed that FGFR4 was upregulated in 20/71 patients independent of g

293 to dissect the molecular pathways involving Fgfr4, we queried the promoter sequences for transcripti

294 pressing beta-Klotho together with FGFR1c or FGFR4 were also analyzed.

295 , namely retention of a single intron within fgfr4 when maternal and zygotic Taf15 is depleted, and r

296 Fgfr4, which encodes the likely receptor for both FGF19

297 d to be highly expressed, including IGF2 and FGFR4, which were both highly expressed and targets of t

298 y, FGF23 increases cardiac contractility via FGFR4, while known effects of FGF23 on aortic relaxation

299 ganoids reveals a synergistic effect of anti-FGFR4 with anti-HER2 therapy in breast cancer with eithe

300 ing constitutively active hepatic FGFR4--and FGFR4(-/-) with constitutively active hepatic FGFR4 rest