ライフサイエンスコーパス: PDGFRB

1 PDGFRB directly phosphorylates multiple novel sites on t

2 PDGFRB pathway involvement was confirmed by the anti-fib

3 PDGFRB small interfering RNA inhibited collagen expressi

4 PDGFRB-variant, but not wild-type, patient cells were fo

5 cally distinct genetic condition caused by a PDGFRB gain-of-function mutation that is associated with

6 iscovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity

7 R::ABL1-like (Ph-like) subtype include ABL1, PDGFRB, ABL2, and CSF1R, each of which has up to 10 desc

8 , Y272, and Y310) to phenylalanine abrogated PDGFRB-mediated activation of Abl2.

9 sm specimens, we detected somatic-activating PDGFRB variants in the juxtamembrane domain or the kinas

10 nic proteins including EGFR, IGF1R, CDK6 and PDGFRB in glioma cells.

11 sdifficile infection, inhibited collagen and PDGFRB messenger RNA (mRNA) expression in CDSE-treated C

12 emic cells expressing ABL1, ABL2, CSF1R, and PDGFRB fusions were sensitive in vitro to dasatinib, EPO

13 ass fusions involving ABL1, ABL2, CSF1R, and PDGFRB that phenocopy BCR-ABL1 and alterations of CRLF2,

14 le ABL-class fusions (ABL1, ABL2, CSF1R, and PDGFRB) in 14.1%, EPOR rearrangements or JAK2 fusions in

15 nriched gene network that includes FGFR3 and PDGFRB.

16 Expression of ABL1, ABL2, CSF1R, JAK2, and PDGFRB fusions resulted in cytokine-independent prolifer

17 h ABL2 fusions (six [86%] of 7 patients) and PDGFRB fusion-positive B-cell acute lymphocytic leukaemi

18 h ABL2 fusions (six [86%] of 7 patients) and PDGFRB fusion-positive B-cell acute lymphocytic leukaemi

19 eosinophilic MPNs associated with PDGFRA and PDGFRB fusion genes are responsive to imatinib.

20 Both PDGF receptor genes (PDGFRA and PDGFRB) also showed no disease associations.

21 d growth factor receptor A and B (PDGFRA and PDGFRB) tyrosine kinases.

22 growth factor receptors a and B (PDGFRa and PDGFRB).

23 the MSC region and interact with PDGFRA and PDGFRB.

24 Significantly, PDGFRA+ and PDGFRB+ cells differentially contribute to defined cell

25 sion of total and activated KIT, PDGFRA, and PDGFRB were assessed using immunohistochemistry and immu

26 between the expression of SDF1, PDGFRA, and PDGFRB, which is upregulated, along CXCR4 in tumor cells

27 The natural history of PDGFRA- and PDGFRB-rearranged neoplasms has been dramatically altere

28 fusion-positive, CSF1R fusion-positive, and PDGFRB fusion-positive) B-cell acute lymphocytic leukaem

29 mutually exclusive PDGFRbeta (also known as PDGFRB) upregulation or N-RAS (also known as NRAS) mutat

30 o known vascular and stromal markers such as PDGFRB, we observed stromal expression of PTK6 and TNS1

31 s platelet-derived growth factor receptor B (PDGFRB) signaling as part of a core response to divergen

32 l platelet-derived growth factor receptor-B (PDGFRB), a pericyte marker, was reduced, and endothelin-

33 ugh PDGFB (platelet-derived growth factor B)-PDGFRB (platelet-derived growth factor receptor beta) si

34 latelet-derived growth factor receptor beta (PDGFRB) in all 11 affected individuals with familial IM,

35 latelet-derived growth factor receptor beta (PDGFRB) in the fibrotic ileal tissues of CDS patients.

36 latelet-derived growth factor receptor beta (PDGFRB) is expressed by adult V-SVZ NSCs that generate o

37 latelet derived growth factor receptor beta (PDGFRB) messenger RNA and protein, enhanced proliferatio

38 latelet-derived growth factor receptor beta (PDGFRB) to the coiled-coil domains of a novel partner pr

39 latelet-derived growth factor receptor beta (PDGFRB)+ progenitor subpopulations are tightly regulated

40 latelet-derived growth factor receptor beta (PDGFRB), are considered causal.

41 latelet-derived growth factor receptor beta (PDGFRB), important for cell proliferation and chemotaxis

42 latelet-derived growth factor receptor beta (PDGFRB), which encodes a receptor tyrosine kinase.

43 related DCM and point to PDGF receptor-beta (PDGFRB) as a potential therapeutic target.

44 Further studies of the crosstalk between PDGFRB and NOTCH pathways may offer new opportunities to

45 orts we show that CD146 is expressed in both PDGFRB + perivascular cells and CD31 + endothelial cells

46 flow induces differentiation of human brain PDGFRB+ mural cells into VSMCs, and blood flow is requir

47 CD31, PDGFRB, and PDGFB all strongly correlate with IBA1+ TAM

48 lysis, the variant rs2302274 located in CDX1/PDGFRB frequently gained/lost in colorectal tumors was a

49 f specific transcription factors controlling PDGFRB (i.e. TP73).

50 Autosomal dominant PDGFRB gain-of-function mutations in mice and humans cau

51 scriptomic changes specifically within DPP4+ PDGFRB+ adipocyte precursor cells, including a B-adrener

52 We report 15 EBF1-PDGFRB-positive patients from childhood ALL treatment tr

53 ons in five of 212 patients, comprising EBF1-PDGFRB, ETV6-ABL1, ZC3HAV1-ABL2, EPOR-IGH, and CNTRL-ABL

54 se findings have prompted screening for EBF1-PDGFRB in patients entered onto the current UKALL 2011 t

55 Two UKALL 2011 patients, positive for EBF1-PDGFRB, received imatinib; 1 died 6 months after a match

56 Prevalence of EBF1-PDGFRB fusions in this group highlights the importance o

57 There are reports of EBF1-PDGFRB-positive patients who are refractory to conventio

58 ce of PDGFRB gene fusions, particularly EBF1-PDGFRB, in almost one third of B-other ALL cases.

59 The EBF1-PDGFRB gene fusion accounts for <1% of B-cell precursor

60 3;p13) translocation associated with an ETV6-PDGFRB fusion gene.

61 In the three patients with the ETV6-PDGFRB fusion gene, the transcript level decreased, and

62 hilia; their leukemia cells carried the ETV6-PDGFRB fusion gene.

63 atrix-including the differentially expressed PDGFRB gene-is involved in morphogenesis, sensitive peri

64 et-derived growth factor receptor beta gene (PDGFRB), a juxtamembrane-coding region.

65 In particular, mutations in six genes (PDGFRB, AHNAK, OBSCN, RBM10, CACNA1E, and OR5P3), many o

66 These findings reveal how PDGFRB engages and phosphorylates Abl2 leading to activa

67 However, PDGFRB phosphorylation was not detected, suggesting that

68 Gain-of-function mutations in human PDGFRB have been linked recently to genetic diseases cha

69 High-throughput screening identified PDGFRB inhibitors that suppressed collagen promoter acti

70 treatment inhibited ileal fibrosis and ileal PDGFRB mRNA expression and PDGFRbeta and GSK3beta phosph

71 p.Pro660Thr) and c.1681C>T (p.Arg561Cys), in PDGFRB.

72 , activating substitution, p.(Asn666Tyr), in PDGFRB.

73 ermore, disrupting mitochondrial function in PDGFRB+ cells rapidly induces alterations in immune cell

74 33 Doxycycline-inducible deletion of Il33 in PDGFRB+ cells at the onset of cold exposure attenuates I

75 h a gain-of-function D849V point mutation in PDGFRB exhibit colony formation defects that parallel th

76 identified a second heterozygous mutation in PDGFRB in two myofibromas from one of the affected famil

77 Our studies suggest that mutations in PDGFRB are a cause of IM and highlight NOTCH3 as a candi

78 Distinct mutations in PDGFRB have been shown to cause infantile myofibromatosi

79 ent, with levels of PPARy phosphorylation in PDGFRB(+) cells inversely correlating with their capacit

80 HIFa suppression in PDGFRB(+) progenitors promotes subcutaneous and intra-ab

81 d a de novo c.1994T>C p.Val665Ala variant in PDGFRB, which encodes the platelet-derived growth factor

82 were shown to have the identical variant in PDGFRB.

83 Somatic gain-of-function variants in PDGFRB are a novel mechanism in the pathophysiology of f

84 urther, de novo gain-of-function variants in PDGFRB, a tyrosine kinase receptor essential for vascula

85 ucing myofibroblasts with markedly increased PDGFRB protein expression and an activated STAT3 signali

86 Here, we reveal that HIFa-induced PDGFRB signaling within murine white adipose tissue (WAT

87 tracing of perivascular cells with inducible PDGFRB and NG2 Cre mouse lines demonstrated that increas

88 ugh a molecular/cellular mechanism involving PDGFRB and associated oncogenic signalling pathways (PI3

89 hilia, and a t(5;12) translocation involving PDGFRB and an unknown partner gene; he also had extensiv

90 Reciprocal translocations involving PDGFRB result in fusion genes with constitutively activa

91 ntified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2, and EPOR, activating mutations of IL7R an

92 le and conditional pericyte depletion mouse (PDGFRB-CreER(T2); ROSA26iDTR) model, we demonstrate, for

93 One child had a CSF1R mutation and MRC1::PDGFRB fusion.

94 e, virus-mediated overexpression of a mutant PDGFRB induced a fusiform-like dilatation of the basilar

95 ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2 and sequence mutations invo

96 ative diseases associated with activation of PDGFRB.

97 causes severe constitutive autoactivation of PDGFRB regardless of temperature.

98 ng the mitochondrial B-oxidative capacity of PDGFRB+ cells via inducible expression of MitoNEET drive

99 omes of substitutions in the Asn666 codon of PDGFRB.

100 Selective deletion of PDGFRB in adult V-SVZ NSCs leads to their release from q

101 sed genes in AD, including downregulation of PDGFRB in pericytes, and of ABCB1 and ATP10A in endothel

102 SRF directs pericyte migration downstream of PDGFRB signaling and mediates pathological pericyte acti

103 y and has been associated with expression of PDGFRB mRNA.

104 AF patients may be mediated by inhibition of PDGFRB kinase activity.

105 to divergent pathogenic fungi; inhibition of PDGFRB reduces Mucorales-induced damage to host cells.

106 Phosphorylation levels of PDGFRB and downstream targets were higher in OPDKD fibro

107 ls of KIT and PDGFRA but expressed levels of PDGFRB that are comparable with normal fibroblasts.

108 n the B-other group revealed the presence of PDGFRB gene fusions, particularly EBF1-PDGFRB, in almost

109 asms and eosinophilia with rearrangements of PDGFRB are uncommon Philadelphia-negative myeloprolifera

110 n cSCC, MM and PDS, with a prominent role of PDGFRB-PDGFD R/L interactions and upregulation of PI3K/A

111 eems preferentially sensitive to SRC/ABL- or PDGFRB-targeting inhibitors.

112 nounced in patient samples harboring FLT3 or PDGFRB alterations.

113 s far been associated with SLC20A2, PDGFB or PDGFRB mutations.

114 ypereosinophilic syndromes without PDGFRA or PDGFRB rearrangements.

115 No mutations of KIT, PDGFRA, or PDGFRB were found.

116 ations in seven genes (SLC20A2, XPR1, PDGFB, PDGFRB, MYORG, NAA60, and JAM2) are associated with PFBC

117 ce of the molecular lesions BCR/ABL, PDGFRA, PDGFRB, and FGFR1.

118 tially expressed in PDX tumors, e.g. PDGFRA, PDGFRB and CSF1R.

119 estigational inhibitor of FLT3, KIT, PDGFRA, PDGFRB and RET; evolution of AC220-resistant substitutio

120 were analyzed for mutations of KIT, PDGFRA, PDGFRB, and CTNNB1 (beta-catenin).

121 lasia, BCR-ABL1 or rearrangements of PDGFRA, PDGFRB or FGFR1.

122 The discovery of PDGFRA, PDGFRB, FGFR1, JAK-2, and FLT3 fusion proteins in patien

123 th eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1') and undefined (chronic eosinophilic l

124 th eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2" In addition to myel

125 ted KIT oncoproteins interacted with PDGFRA, PDGFRB, phosphatidylinositol 3-kinase (PI3-K) and PKCthe

126 apy is currently only observed in MLN-PDGFRA/PDGFRB fusion genes on imatinib.

127 f 4 subjects with phospho-PDGFRA and phospho-PDGFRB immunohistochemistry studies before and after tre

128 sts, equal and high levels of phosphorylated PDGFRB was present at both 32 C and 37 C.

129 xomicin inhibited PDGFRbeta phosphorylation, PDGFRB mRNA expression, and GSK3beta phosphorylation in

130 e DFSPs included PDGF beta and its receptor, PDGFRB, APOD, MEOX1, PLA2R, and PRKCA.

131 In the past 2 years, 3 genes (SLC20A2, PDGFRB, and PDGFB) were identified as causative of prima

132 s, reduces cell proliferation and suppresses PDGFRB expression.

133 TEL-PDGFRB-mediated MPD was incompletely penetrant in TPiGFP

134 ive disease identical to that induced by TEL-PDGFRB alone.

135 nes were refractory to transformation by TEL-PDGFRB in methylcellulose colony assays.

136 ansduced murine bone marrow coexpressing TEL-PDGFRB and AE into lethally irradiated syngeneic mice.

137 family member Stat1 were dispensable for TEL-PDGFRB disease.

138 her Stat5a or Stat5b alone also impaired TEL-PDGFRB-mediated transformation.

139 demonstrating significant sensitivity of TEL-PDGFRB-induced MPD to the dosage of Stat5a.

140 nd Stat5b are dose-limiting mediators of TEL-PDGFRB-induced myeloproliferation.

141 l-culture systems, and expression of the TEL-PDGFRB fusion gene induces myeloproliferative disease (M

142 The TEL-PDGFRB fusion oncogene is associated with chronic myelom

143 scription (Stat) and Src family genes to TEL-PDGFRB-mediated transformation in methylcellulose colony

144 contrast, control mice coexpressing with TEL-PDGFRB and a DNA-binding-mutant of AE developed a nontra

145 n silico survival analysis demonstrated that PDGFRB informed poor prognosis, while PDGFRA was a posit

146 We also found that PDGFRB-mediated phosphorylation of Abl2 in vitro activat

147 horylation was not detected, suggesting that PDGFRB is only weakly activated.

148 In contrast, the PDGFRB-fused ALL samples were less sensitive to dasatini

149 erized by activating mutations of either the PDGFRB or the PDGFRA gene.

150 irectly binds to phosphotyrosine Y771 in the PDGFRB cytoplasmic domain.

151 consequence of this causative variant on the PDGFRB signaling pathway by transfecting mutant and wild

152 gly, one family did not have either of these PDGFRB mutations but all affected individuals had a c.45

153 ted with the cytokine network, of which two (PDGFRB and ABO) had not been detected previously.

154 pericyte-like cells from lung digests using PDGFRB as a selection marker were expanded in culture as

155 Levels of PPARy S112 phosphorylation in WAT PDGFRB(+) cells are depot dependent, with levels of PPAR

156 ing within murine white adipose tissue (WAT) PDGFRB(+) cells drives inhibitory serine 112 (S112) phos

157 64 (52%) of 122 patients were PDGFRB fusion-positive, 40 (33%) were ABL1 fusion-positi

158 rgrowth syndrome), but it is unclear whether PDGFRB mutations alone are responsible.

159 However, the molecular mechanism by which PDGFRB engages and activates Abl family kinases is not k

160 cellent long-term responses in patients with PDGFRB rearrangements.

161 erved when ARPKD organoids were treated with PDGFRB inhibitors.