ライフサイエンスコーパス: FGFR2

1 site on fibroblast growth factor receptor 2 (FGFR2).

2 cally targeted genes (e.g. PIK3CA, ERBB2 and FGFR2).

3 way members and the receptor tyrosine kinase FGFR2.

4 NSCLC driven by a kinase domain mutation in FGFR2.

5 and with variants in AXIN2, FGF3, FGF10, and FGFR2.

6 ing a risk haplotype in the second intron of FGFR2.

7 tion of PTEN on tyrosine 240 (pY240-PTEN) by FGFR2.

8 s a more prominent role in this process than FGFR2.

9 munohistochemistry (FGFR1, 30% positive; and FGFR2, 65% positive) and the CCA cell lines assayed by W

10 total of 11 SNPs from eight genomic regions (FGFR2, 9q31.2, MAP3K, CCND1, ZM1Z1, RAD51L11, ESR1 and U

11 Moreover, signaling through FGFR2, a known risk factor in breast cancer development,

12 Phosphorylation of Grb2 by FGFR2 abrogated its binding to the receptor, resulting i

13 n BBDS, which amplify nucleolar targeting of FGFR2, activate ribosomal DNA (rDNA) transcription and d

14 Nucleolar FGFR2 activates rDNA transcription via interactions with

15 We demonstrate that the mechanism of FGFR2 activation and subsequent transformation is mediat

16 rethra are controlled by discrete regions of Fgfr2 activity.

17 and development of VUR and the mechanisms of Fgfr2 activity.

18 Here, we investigated whether Fgfr2 acts specifically in peri-Wolffian duct stroma (ST

19 In FGFR2-expressing cancer cell lines, this FGFR2-ADC exhibited potency in the low nanomolar to subn

20 Efficacy studies demonstrated that FGFR2-ADC treatment leads to a significant tumor growth

21 s indicated that the toxophore metabolite of FGFR2-ADC was enriched more than 30-fold in tumors compa

22 tubule-disrupting cytotoxic drug auristatin (FGFR2-ADC).

23 r, the increased risk conferred by the minor FGFR2 allele associates most strongly in oestrogen recep

24 Mice missing one allele of Fgfr2 also had (less severe) regeneration defects and ba

25 and fibroblast growth factor receptor gene (FGFR2), among others.

26 Patients' tumors harbored FGFR1 or FGFR2 amplification (n = 20), FGFR2 or FGFR3 single-nucl

27 Furthermore, FGFR2 amplification or mRNA overexpression predicted hig

28 ng mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endome

29 found ligand-independent phosphorylation of FGFR2 and activation of p38 signaling in mutant skin and

30 he oncogenic nature of mutations observed in FGFR2 and FGFR3, each of which are observed in 3% of sam

31 ve genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS on

32 mediate at least in part the signaling from FGFR2 and FGFR3.

33 FGF10 is an oncogene that binds to FGFR2 and is overexpressed in approximately 10% of human

34 electively reduced plasma-membrane levels of FGFR2 and markedly diminished the receptor's responsiven

35 FGFR2 and other FGFR kinase family gene alterations have

36 Our results indicate that FGFR2 and PAPSS2 may play an important role in the regul

37 Both reciprocal activities of FGFR2 and Shp2 were inhibited by binding of Grb2 to the

38 ol over the mutually dependent activities of FGFR2 and Shp2.

39 ibit amplified expression of FGF receptor 2 (FGFR2) and are dependent on continued FGFR2 signalling f

40 he fibroblast growth factor receptor 2 gene (FGFR2) and the TOC high mobility group box family member

41 EN, EGFR, RAD51, ALKBH2, BRCA1, ERBB2, TP53, FGFR2, and CTNND1.

42 FGF receptor (FGFR) KO mice; however, FGFR1, FGFR2, and FGFR3 KO mice did not mimic the phenotype of

43 ee fibroblast growth factor receptors-FGFR1, FGFR2, and FGFR3-in the absence of ligand.

44 kely receptor mediated, albeit not by FGFR1, FGFR2, and FGFR3.

45 etable mutations in SMO, DDR2, FGFR1, PTCH1, FGFR2, and MET Our results indicate that a significant p

46 HA2-FGFR2, EPHA2-FGFR3, VEGFR2-FGFR1, VEGFR2-FGFR2, and VEGFR2-FGFR3, using a FRET-based method.

47 neurons, while its main receptors FGFR1 and FGFR2 are expressed by cortical projection neurons.

48 Somatic mutations in FGFR2 are present in 4% to 5% of patients diagnosed with

49 FGF receptors 1 and 2 (Fgfr1 and Fgfr2) are both expressed in the osteoprogenitor lineage

50 Identifying FGFR2 as a transcriptional regulator of rDNA in bone une

51 ased hepatic expression of FGF10, FGFR1, and FGFR2 as well as mesenchymal genes SLUG and SNAIL.

52 within fibroblast growth factor receptor 2 (FGFR2) as one of the highest ranking risk alleles in ter

53 They also provide the stem cell regulator, FGFR2, as a promising candidate target for future SS the

54 the fibroblast growth factor receptor gene, Fgfr2, as one occupied and upregulated by SYT-SSX2.

55 s to be driven largely by FGF5 activation of FGFR2, as siRNA silencing of this ligand or receptor, re

56 al signaling, enhance nucleolar occupancy of FGFR2 at the ribosomal DNA (rDNA) promoter.

57 Aberrant splicing of Fgfr2 blocked stria vascularis formation due to erroneou

58 ity of a neural crest enhancer downstream of FGFR2 both in vitro and in vivo.

59 tion of fibroblast growth factor receptor 2 (Fgfr2) broadly in renal and urinary tract mesenchyme led

60 petent avian sarcoma virus expressing either FgfR2(C278F), a receptor mutation found in Crouzon syndr

61 Embryonic knockout of FGFR2 causes a reduction of hippocampal volume and impai

62 to Ctnnb1(cnull) mutation) or expand (due to Fgfr2(cnull) mutation) early respiratory endodermal prog

63 Mutations in FGFR2 could possibly cause VUR in humans.

64 Mechanistically, FGF23 binding to FGFR2 counteracted selectin- and chemokine-triggered bet

65 G1, TPM3-NTRK1 and RUFY2-RET in lung cancer, FGFR2-CREB5 in cholangiocarcinoma and PPL-NTRK1 in thyro

66 FGFR2 cycles between its kinase-active, partially phosph

67 wn to regulate myelin thickness, we examined FGFR2-deficient mice for the expression of key signaling

68 To test this hypothesis, we mated the Fgfr1-/Fgfr2-deficient mice with mast cell-deficient CreMaster

69 and degranulated in the skin of young Fgfr1-/Fgfr2-deficient mice, most likely as a consequence of in

70 Using Fgfr1-/Fgfr2-deficient mice, we analyzed the consequences of th

71 sults in two distinct phenotypes: endodermal Fgfr2 deletion causes mild hypospadias and inhibits matu

72 Fgfr2 deletion in the ocular surface epithelium reduced

73 Basal cells lacking Fgfr2 did not generate an epithelial network owing to a

74 s are separate from previously characterized FGFR2 disorders and represent a distinct skeletal dyspla

75 We show that Fgfr1 and Fgfr2 double knockouts (FGFR DKO) generated by Cre-media

76 This is the first FGFR2-driven lung cancer GEMM, which can be applied acro

77 role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hind

78 ously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-p

79 tion among patients with malocclusion, while FGFR2, EDN1, TBX5, and COL1A1 are associated with type o

80 three loci with putative regulation events (FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in

81 last growth factor receptor 1 (FGFR1), EPHA2-FGFR2, EPHA2-FGFR3, VEGFR2-FGFR1, VEGFR2-FGFR2, and VEGF

82 r, they support the importance of TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in human lung org

83 Most recently, disruption of the TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling pathway has been

84 Thus, reduced FGFR2/ERK signaling apparently leads to abnormal urothel

85 In FGFR2-expressing cancer cell lines, this FGFR2-ADC exhib

86 ll cell populations of the blastocyst, while Fgfr2 expression becomes restricted to extraembryonic li

87 ults in impaired Hippo signaling and reduced Fgfr2 expression both of which control stem cell functio

88 f10 expression in the adjacent mesenchyme or Fgfr2 expression in the epithelium, but appeared to redu

89 We identify and characterize novel FGFR2 extracellular domain insertion mutations and demon

90 e or Tie2-Cre mediated deletion of FGFR1 and FGFR2 (Fgfr1/2(Flk1-Cre) or Fgfr1/2(Tie2-Cre) mice), whi

91 Conditional urothelial deletion of Fgfr2 (Fgfr2KO) did not affect injury severity or prolif

92 cer tumorigenesis include IDH1, IDH2, FGFR1, FGFR2, FGFR3, EPHA2, BAP1, ARID1B, ELF3, PBRM1, PRKACA,

93 ene fusion panel including ALK, BRAF, FGFR1, FGFR2, FGFR3, MET, NRG1, NTRK1, NTRK2, NTRK3, RET and RO

94 wever, have normal kidneys; the roles of the Fgfr2/Frs2alpha signaling axis in MM development and reg

95 ken together, these results demonstrate that Fgfr2/Frs2alpha signaling in the MM promotes Bmp4 expres

96 active fibroblast growth factor receptor 2 (FGFR2) fusion proteins (FFs) generated by chromosomal tr

97 spib combo improves therapeutic targeting of FGFR2 fusions in an experimental setting, which may be r

98 38 (35.5% [95% CI 26.5-45.4]) patients with FGFR2 fusions or rearrangements achieved an objective re

99 , 2019, 146 patients were enrolled: 107 with FGFR2 fusions or rearrangements, 20 with other FGF/FGFR

100 ieved an objective response among those with FGFR2 fusions or rearrangements, assessed centrally in a

101 igned to one of three cohorts: patients with FGFR2 fusions or rearrangements, patients with other FGF

102 tastatic cholangiocarcinoma with and without FGFR2 fusions or rearrangements.

103 ed patients with cholangiocarcinoma who have FGFR2 fusions or rearrangements.

104 f a cohort of 107 iCCA patients reveals that FGFR2 fusions represent the most recurrent targetable al

105 t least one actionable molecular alteration (FGFR2 fusions, IDH1/2, ARAF, KRAS, BRAF and FGF19) that

106 eted therapeutically, such as fusions in the FGFR2 gene and mutations in genes encoding isocitrate de

107 Heterozygous mutations in the human FGFR2 gene cause various craniosynostosis syndromes incl

108 nt for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independen

109 rs1219648, which annotates the FGFR2 gene, was associated with risk in both series (com

110 ephosphorylation of Grb2 by Shp2 rescued the FGFR2-Grb2 complex.

111 FGF receptor 2 (FGFR2) has a significant role in the production of corti

112 FGF-10 and its receptors, FGFR1 and FGFR2, have been implicated in breast cancer susceptibil

113 turn, inhibits TRPA1-mediated activation of FGFR2, hindering the metastatic process.

114 FR1c2 HS binding sites of the symmetric FGF2-FGFR2-HS2 signal transduction complex.

115 sette exons that generate receptor variants (FGFR2 IIIb or IIIc) with different ligand specificities.

116 the fibroblast growth factor (FGF) receptor FGFR2-IIIb and FGFR2-IIIc varying their extracellular st

117 1179470), which binds to the FGFR2 isoforms FGFR2-IIIb and FGFR2-IIIc, conjugated through a noncleav

118 Conversely, FGFR2-IIIb expression in epithelial cells yielded higher

119 Enforced expression of either FGFR2-IIIb or FGFR2-IIIc in thyroid epithelial cancer ce

120 Enforced expression of either FGFR2-IIIb or FGFR2-IIIc in thyroid epithelial cancer cells reduced ex

121 growth factor (FGF) receptor FGFR2-IIIb and FGFR2-IIIc varying their extracellular structure in huma

122 h binds to the FGFR2 isoforms FGFR2-IIIb and FGFR2-IIIc, conjugated through a noncleavable linker to

123 GF4/FGF7 expression that, in the presence of FGFR2-IIIc-expressing fibroblasts, enhanced tumor progre

124 Deletion of either Fgf9 or Fgfr2 in an XY gonad resulted in up-regulation of Wnt4 a

125 An increase in the nucleolar activity of FGFR2 in BBDS elevates levels of ribosomal RNA in the de

126 Knockdown of FGFR2 in both BMMSCs and SS cells abrogated their growth

127 981578, resulting in increased expression of FGFR2 in cancers from patients homozygous for that allel

128 High expression levels of FGFR2 in cells correlated with efficient internalization

129 s establish combinatorial roles of Fgfr1 and Fgfr2 in development and uncouple novel FGFR kinase-depe

130 pment by generating conditional deletions of Fgfr2 in each of these cell types.

131 FGFR1 again having a greater influence than FGFR2 in ESC exit from the pluripotent state.

132 we investigate the tissue-specific roles of Fgfr2 in external genital development by generating cond

133 Here, we have examined the requirement of Fgfr2 in mouse mammary gland morphogenesis using a postn

134 mice lacking both FGF receptor 1 (Fgfr1) and Fgfr2 in oligodendrocyte-lineage cells but found that in

135 We conditionally deleted Fgfr2 in ST (Fgfr2(ST-/-)) using Tbx18cre mice.

136 er, our data highlight a pleiotropic role of Fgfr2 in stem cell differentiation and branch initiation

137 vere hypospadias highlights a major role for Fgfr2 in the developing genital surface epithelium, wher

138 ciency or the targeted deletion of FGFR1 and FGFR2 in the hindlimb motor cortex limits the formation

139 Here we dissociate the role of FGFR2 in the hippocampus during development and during a

140 Unlike mice lacking both Fgfr1 and Fgfr2 in the MM, these mice had no obvious MM defects bu

141 We find that loss of Fgfr2 in the mouse tendon-bone interface reduces Scx exp

142 in which FGFs, possibly from axons, activate FGFR2 in the oligodendrocyte/myelin compartment to incre

143 we show that specific deletion of Fgfr1 and Fgfr2 in the optic vesicle disrupts ERK signaling, which

144 Mice with conditional deletion of Fgfr2 in urothelium enriched for KRT14(+) cells reproduc

145 ionally deleting one copy of FGF receptor 2 (FGFR2) in adult mouse airway basal cells results in self

146 ream of fibroblast growth factor receptor 2 (Fgfr2) in regulating early calvarial osteogenic differen

147 Furthermore, deletion of Fgf receptor 2 (Fgfr2) in the epithelium also leads to significantly red

148 dysplasia syndrome (BBDS) demonstrates that FGFR2, in addition to its canonical signaling activities

149 bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the recept

150 FGFR2 inhibition by SU5402 impacts a significant fractio

151 fining mechanisms of intrinsic resistance to FGFR2 inhibition.

152 g axis in endogenous SCCs using the clinical FGFR2 inhibitor AZD4547.

153 ich is successfully inhibited by a selective FGFR2 inhibitor in vitro.

154 We identified EFNB2, FGFR1, FGFR2, INSR, IRS2, NOTCH2, TLE1, and NTRK2 as novel mark

155 Here the authors propose that TRPA1/FGFR2 interaction is functional in LUAD and show that as

156 howed that the alternative splicing event of FGFR2 is associated with virus infection, tumor size, ci

157 We confirmed that Fgfr2 is expressed in ST and that Fgfr2 was efficiently

158 bryonic precursor of the penis and clitoris, Fgfr2 is expressed in two epithelial populations: the en

159 The fibroblast growth factor receptor FGFR2 is overexpressed in a variety of solid tumors, inc

160 Among these genes, we show Fgfr2 is required for adrenal rosette formation by regul

161 779) in the cytoplasmic domains of FGFR1 and FGFR2 is required for the sustained activation of Ras an

162 The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estroge

163 Here, we show that FGF receptor type 2 (FGFR2) is highly enriched at the paranodal loops of myel

164 t ectopic expression of GATA6, together with FGFR2 isoform IIIb, increases anchorage-independent grow

165 tibody (mAb BAY 1179470), which binds to the FGFR2 isoforms FGFR2-IIIb and FGFR2-IIIc, conjugated thr

166 Despite the PrE-specific expression of FGFR2, it is FGFR1, expressed by all ICM cells, that is

167 even of nine Src family kinase genes, FGFR1, FGFR2, ITK, NTRK1, NTRK2, MOS, MST1R, and RAF1.

168 roblast growth factor receptor 1 (Fgfr1) and Fgfr2 (K5-R1/R2 mice) in the epidermis have a severe imp

169 d, and divergent, responses to inhibition of FGFR2 kinase activity in the canonical RAF/MAPK/ERK/RSK

170 d-independent dimerization and activation of FGFR2 kinase activity.

171 ch RTK, fibroblast growth factor receptor 2 (FGFR2) kinase, is still unknown, as the numerous crystal

172 d inhibitor cross-activities between PKR and FGFR2 kinases.

173 alterations in ALK, ARAF, BRAF, EGFR, FGFR1, FGFR2, KIT, KRAS, MAP2K1, MET, NF1, NF2, NRAS, RAF1, RET

174 at mutations in the extracellular domains of FGFR2 lead to constitutive FGFR dimerization.

175 The associations at the FGFR2 locus were also weakly replicated in a dataset fro

176 allele-imbalanced manner to the fSNPs on the FGFR2 locus.

177 The fibroblast growth factor receptor 2 (FGFR2) locus has been consistently identified as a breas

178 Furthermore, in vivo Fgfr2 loss-of-function in the ectoderm caused derepressi

179 d mice with both Fgfr1 deleted in the MM and Fgfr2(LR/LR) point mutations (Fgfr1(Mes-/-)Fgfrf2(LR/LR)

180 ding site for the docking protein Frs2alpha (Fgfr2(LR/LR)), however, have normal kidneys; the roles o

181 date fSNPs on three well-characterized loci: FGFR2, MAP3K1 and BABAM1.

182 However, the molecular mechanisms underlying FGFR2-mediated risk are still unknown.

183 d a preponderance of cancer genes, including FGFR2, MEN1, HOOK3, EZH2, MLF1, CARD11, VHL, NONO, and S

184 Fibroblast growth factor receptor 2 (FGFR2) might have an important role in the pathogenesis

185 In contrast, in the asymmetric FGF2-HS1-FGFR2 model, a single HS chain interacts with the FGF2-F

186 In the symmetric FGF2-HS2-FGFR2 model, two acidic HS chains bind in a basic canyon

187 Dimeric Grb2 binds to the C termini of two FGFR2 molecules.

188 It consists of a fully human FGFR2 monoclonal antibody (mAb BAY 1179470), which binds

189 nerated allelic series of knock-in Fgfr1 and Fgfr2 mouse strains, carrying point mutations that disru

190 ssed the induction of HER3, InsR, IGF1R, and FGFR2 mRNAs upon inhibition of PI3K.

191 Second-line dovitinib in FGFR2(mut) and FGFR2(non-mut) advanced or metastatic end

192 ith FGFR2 prescreening results, 27 (11%) had FGFR2(mut) endometrial cancer.

193 Dec 13, 2013, we enrolled 22 patients in the FGFR2(mut) group and 31 patients in the FGFR2(non-mut) g

194 en (31.8%, 95% CI 13.9-54.9) patients in the FGFR2(mut) group and nine (29.0%, 14.2-48.0) in the FGFR

195 seven (35%) of the first 20 patients in the FGFR2(mut) group were progression free at 18 weeks, as w

196 s, as were five (25%) of the first 20 in the FGFR2(mut) population.

197 therapy both in patients with FGFR2-mutated (FGFR2(mut)) endometrial cancer and in those with FGFR2-n

198 ot the formation, of tetrads and rosettes in Fgfr2 mutant limb-bud ectoderm.

199 titutions: the C178S FGFR1 mutant, the C342R FGFR2 mutant, and the C228R FGFR3 mutant.

200 rapeutically targeting this unique subset of FGFR2-mutant cancers as well as insight into their oncog

201 Both FGFR2-mutant forms are predominantly located in the endo

202 f Wnt4 could rescue sex reversal in Fgf9 and Fgfr2 mutants.

203 as second-line therapy both in patients with FGFR2-mutated (FGFR2(mut)) endometrial cancer and in tho

204 In addition, we report a patient with an FGFR2-mutated oral SCC who responded to the multitargete

205 In summary, this study identifies the first FGFR2 mutation in a 46,XY GD patient.

206 We grouped women according to FGFR2 mutation status and gave all women dovitinib (500

207 rved treatment effects seemed independent of FGFR2 mutation status.

208 Activating FGFR2 mutations are found in 10-16% of primary endometri

209 Inhibition of p53 in cells expressing the FGFR2 mutations in BBDS rescues delayed osteoblast diffe

210 We previously showed that FGFR2 mutations in BBDS, which amplify nucleolar targeti

211 By studying dominant FGFR2 mutations that are germline in bent bone dysplasia

212 Previously, we showed that the unique FGFR2 mutations that cause BBDS reduce receptor levels a

213 sorders, including Apert syndrome (caused by FGFR2 mutations), achondroplasia, and thanatophoric dysp

214 and was more than 100-fold selective against FGFR2-negative cell lines.

215 Second-line dovitinib in FGFR2(mut) and FGFR2(non-mut) advanced or metastatic endometrial cancer

216 to be treatment-related: one patient in the FGFR2(non-mut) group died from cardiac arrest with contr

217 ut) group and nine (29.0%, 14.2-48.0) in the FGFR2(non-mut) group were progression-free at 18 weeks.

218 the FGFR2(mut) group and 31 patients in the FGFR2(non-mut) group.

219 cancer and in those with FGFR2-non-mutated (FGFR2(non-mut)) endometrial cancer.

220 2(mut)) endometrial cancer and in those with FGFR2-non-mutated (FGFR2(non-mut)) endometrial cancer.

221 Moreover, Fgfr2 null epithelium was unable to undergo ductal branc

222 to class I with the minor alleles of SNPs in FGFR2 (odds ratio [OR] = 2.1, P = 0.004) and declined wi

223 elium, and downregulation of FGF receptor 2 (FGFR2) on PMNs rescued host defense in these mice.

224 bored FGFR1 or FGFR2 amplification (n = 20), FGFR2 or FGFR3 single-nucleotide variants (n = 19), or F

225 urothelial and endometrial cancer (all with FGFR2 or FGFR3 translocations); 16 patients had stable d

226 Deletion of Fgfr2 or its ligand Fgf10 results in severe hypospadias

227 Patients with genetic variants in FGFR2 or its ligands may have increased risks of hemorrh

228 I risk increased versus class I with SNPs in FGFR2 (OR 2.2, P = 0.005) and COL1A1 (OR = 2.1, P = 0.00

229 lls, in which any one of three FGFRs (FGFR1, FGFR2, or FGFR3) is sufficient for survival.

230 ry AMs appear to harbor more frequently RAS, FGFR2, or SMO mutations.

231 ne novel locus associated with TG near WDR11-FGFR2 (P = 2.7 x 10-10).

232 reas 2 NRAS (p.Q61R), 2 HRAS (p.Q61R), and 2 FGFR2 (p.C383R) activating mutations were identified in

233 Concurrently, Shp2 cycles between its FGFR2-phosphorylated and dephosphorylated forms.

234 this background cycling, promoting increased FGFR2 phosphorylation and kinase activity, Grb2 dissocia

235 trate that differential expression levels of FGFR2, Plcgamma1 and Grb2 correlate with patient surviva

236 tro Pharmacokinetic analyses in mice bearing FGFR2-positive NCI-H716 tumors indicated that the toxoph

237 ng analyses, we report a novel fusion event, FGFR2-PPHLN1 (16%), and damaging mutations in the ARAF o

238 l translocation t(10;12)(q26;q12) leading to FGFR2-PPHLN1 fusion possesses transforming and oncogenic

239 impairs its ability to bind to its substrate FGFR2 pre-mRNA.

240 Of 248 patients with FGFR2 prescreening results, 27 (11%) had FGFR2(mut) endo

241 Fibroblast growth factor receptor 2 (FGFR2) promotes osteoprogenitor proliferation and differ

242 l, a single HS chain interacts with the FGF2-FGFR2 protein complex through a single S-domain that can

243 c canyon located on the top face of the FGF2-FGFR2 protein complex.

244 hains are proposed to interact with the FGF2-FGFR2 protein complex.

245 otspots in the tyrosine kinase domain of the FGFR2 protein, one of which is also a hotspot in breast

246 lates cell cycle exit via components of FGF (Fgfr2, Prox1 and Ccnd1) and Wnt (Dkk3, Wnt7a, Lrp6, Bcl9

247 Using model systems we show that FGFR2-regulated genes are preferentially linked to breas

248 Here, we show that Fgfr2 regulates both the formation and resolution of tet

249 al anomalies, cellular analysis reveals that Fgfr2 regulates epithelial maturation and cell cycle pro

250 se features we would suggest represent a new FGFR2-related syndrome, craniosynostosis with XY male-to

251 thral epithelium, whereas loss of ectodermal Fgfr2 results in severe hypospadias and absence of the v

252 expected finding that ectodermal deletion of Fgfr2 results in the most severe hypospadias highlights

253 Conditional deletion of Fgfr2 results in two distinct phenotypes: endodermal Fgf

254 , we reveal a mechanistic connection between FGFR2, ribosome biogenesis, and cellular stress that lin

255 ocus is consistent with the finding that the FGFR2 risk locus primarily predisposes to estrogen-recep

256 d were with imputed SNPs residing within the FGFR2 (rs1219515, P = 1.1 x 10(-5)) and PAPSS2 (rs196982

257 iduals who carried the polymorphic allele of FGFR2 (rs1219648) presented higher risk for having premo

258 68277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (M

259 Mice with point mutations in Fgfr2's binding site for the docking protein Frs2alpha (

260 receptor, resulting in up-regulation of both FGFR2's kinase and Shp2's phosphatase activity.

261 unanticipated role for p63-driven paracrine FGFR2 signaling as an addicting pathway in human cancer

262 ormation and suggests that the miR-327-FGF10-FGFR2 signaling axis may be a therapeutic targets for tr

263 netic contexts, maintaining normal levels of FGFR2 signaling is important for human testis determinat

264 a feedback loop induced by MEK inhibition on FGFR2 signaling pathway.

265 mor-survival program involving p63-regulated FGFR2 signaling that was activated by ligand emanating f

266 tween two developmental pathways affected by FGFR2 signaling, possibly offering a junction to exploit

267 phenotype that can be reverted by inhibiting FGFR2 signaling.

268 ontrols fibroblast growth factor receptor 2 (FGFR2) signaling by regulating receptor kinase and SH2 d

269 We show that FGFR2 signalling correlates with maintenance of expressi

270 tor 2 (FGFR2) and are dependent on continued FGFR2 signalling for cell viability.

271 uggesting that ERK1/2 are key transducers of FGFR2 signals for myelin growth.

272 Analysis of the FGFR2-skeletal disorder bent bone dysplasia syndrome (BB

273 r2 was efficiently deleted in this tissue in Fgfr2(ST-/-) mice at embryonic day (E) 10.5.

274 le ureters were histologically normal, E15.5 Fgfr2(ST-/-) mice exhibit improper ureteral insertion si

275 E10.5 Fgfr2(ST-/-) mice had decreases in Bmp4 mRNA in stromal

276 E11.5 Fgfr2(ST-/-) mice had randomized UB induction sites with

277 We conditionally deleted Fgfr2 in ST (Fgfr2(ST-/-)) using Tbx18cre mice.

278 with HSP90 blockade by ganetespib suppressed FGFR2-TACC3 (transforming acidic coiled-coil containing

279 neous tumors generated by transplantation of FGFR2-TACC3 NIH3T3 transformants.

280 sed signaling models, the symmetric FGF2-HS2-FGFR2 ternary complex model and the asymmetric FGF2-HS1-

281 port a preference for the symmetric FGF2-HS2-FGFR2 ternary complex model.

282 ry complex model and the asymmetric FGF2-HS1-FGFR2 ternary complex model.

283 aling effectors, and a kinase dead allele of Fgfr2 that broadly phenocopies the null mutant.

284 on was able to interact with the promoter of FGFR2, the likely target gene of this risk region.

285 mouse embryos heterozygous for Tbx1 or Fgfr1/Fgfr2 to hypoxia in utero increased the incidence and se

286 at the BBDS mutations augment the ability of FGFR2 to recruit histone-remodeling factors that epigene

287 the alternative splicing of FGF receptor-2 (FGFR2) transcripts, altering the incorporation of casset

288 nstrate fibroblast growth factor receptor 2 (FGFR2) triggers Nanog gene down-regulation and different

289 irmed that Fgfr2 is expressed in ST and that Fgfr2 was efficiently deleted in this tissue in Fgfr2(ST

290 n the dentate gyrus were deficient even when FGFR2 was lacking only in adulthood.

291 FGF4 ligand and FGFR2 were detected primarily on the plasma membrane of

292 s, and 14 markers in AXIN2, FGF3, FGF10, and FGFR2 were genotyped.

293 ences in allele specific expression (ASE) of FGFR2 were not observed in a panel of 72 ERalpha positiv

294 for this transcriptional down-regulation by FGFR2, when the reporter transgenes were integrated with

295 t observed by LM-PCR (Myc, Akt1, Pth, Csf1r, Fgfr2, Wisp1, Map3k5, and Map4k3).

296 tly, it provides compelling evidence linking FGFR2 with the ERK1/2-MAPK pathway, which converges with

297 associations between AXIN2, FGF3, FGF10, and FGFR2 with tooth agenesis [i.e., individuals who carried

298 unique and additive activities of FGFR1 and FGFR2 within the ICM coordinate establishment of two dis

299 XY Fgf9/Wnt4 and Fgfr2/Wnt4 double mutants developed testes with male som

300 Fgfr2+/Y394C mice exhibited epidermal hyperplasia and pr

301 cally, they show how alternative splicing of FGFR2 yields heteroisoforms critical to the growth-promo