ライフサイエンスコーパス: IGFBP-5

1 IGF-binding proteins (IGFBP-2, IGFBP-3, and IGFBP-5).

2 nsulin-like growth factor binding protein-5 (IGFBP-5).

3 lation, and a key player in this paradigm is IGFBP-5.

4 teolysis restored the potentiating effect of IGFBP-5.

5 it increased the proteolytic degradation of IGFBP-5.

6 reatments increased concentrations of intact IGFBP-5.

7 analogue, R(3)-IGF-1, which binds weakly to IGFBP-5.

8 and the eluant was fully active in cleaving IGFBP-5.

9 were performed without chemical reduction of IGFBP-5.

10 sts secrete C1r and C1s that actively cleave IGFBP-5.

11 s of IGFBPs, including IGFBP-2, IGFBP-4, and IGFBP-5.

12 entified it as the 3'-untranslated region of IGFBP-5.

13 es it difficult to assess the role of intact IGFBP-5.

14 pSMC cultures that were producing the mutant IGFBP-5.

15 4A/Rl36A mutant complexes compared to native IGFBP-5.

16 a MAPK-dependent manner and bound to nuclear IGFBP-5.

17 he extracellular matrix-promoting effects of IGFBP-5.

18 ave definitively mapped 5 disulfide bonds in IGFBP-5.

19 The mutant IGFBP-5 (500 ng/ml) decreased IGF-I stimulated cellular

20 transcriptional factor(s) that interact with IGFBP-5, a human aorta cDNA library was screened by a ye

21 The mutant IGFBP-5 accumulated in culture medium of transfected cel

22 urs independently of IGF-I, and results from IGFBP-5 activation of MAPK signaling, which facilitates

23 In order to examine whether IGFBP-5 acts by inhibiting the survival effect of IGF-I

24 cation-deficient adenovirus expressing human IGFBP-5 (Ad5), IGFBP-3 (Ad3), or no cDNA (cAd) to wild-t

25 5 adenovirus expressing human IGFBP-3 (Ad3), IGFBP-5 (Ad5), or no complementary DNA (cAd).

26 Furthermore, the addition of exogenous IGFBP-5 alone increased apoptosis.

27 IGFBP-5 also induced migration of peripheral blood monon

28 IGFBP-5 also regulates these cellular events through IGF

29 to fragments, PSMC overexpressing the mutant IGFBP-5 also responded poorly to IGF-I compared with moc

30 tralizing antibody, it was demonstrated that IGFBP-5 also stimulates VSMC migration in an IGF-indepen

31 IGFBP-5 also stimulates VSMC migration through an IGF-in

32 IGFBP-5 and -6 mRNAs, undetectable in control cells, wer

33 roughout the pouch, but was coexpressed with IGFBP-5 and alpha-subunit in the ventral portion of the

34 mplexes or ternary complexes with IGFBP-3 or IGFBP-5 and an acid-labile subunit (ALS).

35 To demonstrate a causal relationship between IGFBP-5 and cell death we created transgenic mice expres

36 d IGFBP-5 confirmed that interaction between IGFBP-5 and FHL2 occurs in whole cells.

37 ide new insights into the mechanisms whereby IGFBP-5 and FLNa exert intranuclear effects.

38 The complex formation of IGFBP-5 and FN was established by glutathione S-transfer

39 esult in an increase in the amount of intact IGFBP-5 and IGF-1 in cartilage and joint fluid, and whet

40 s and the outflow pathway, the expression of IGFBP-5 and IGF-I receptor in the TM was characterized.

41 IGFBP-5 and IGF-I receptor were expressed at significant

42 positive feedback mechanism therefore links IGFBP-5 and IGF-I secretion that reinforces their indivi

43 , cytoskeleton, and the pro-myogenic factors Igfbp-5 and Igf2 were down-regulated.

44 (IGFBP-5), as it was mimicked by recombinant IGFBP-5 and mitigated by neutralizing IGFBP-5 antibody.

45 nding assays using glutathione S-transferase-IGFBP-5 and native IGFBP-5 in vitro and by co-immunoprec

46 an intracellular mediator of the effects of IGFBP-5 and other osteoregulatory agents in osteoblasts

47 n medium, we determined the cleavage site in IGFBP-5 and prepared a protease resistant mutant.

48 duction of nuclear Egr-1 that interacts with IGFBP-5 and promotes fibrotic gene transcription.

49 esults in increased concentrations of intact IGFBP-5 and that proteolysis of IGFBP-3 is also inhibite

50 s, ternary complex formation with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit,

51 evaluate the protein expression patterns of IGFBP-5 and the IGF-I receptor.

52 nsulin-like growth factor-binding protein-5 (IGFBP-5) and insulin-like growth factor-I (IGF-I) are pr

53 nsulin-like growth factor binding protein-5 (IGFBP-5) and their responsiveness to insulin-like growth

54 binant IGFBP-5 and mitigated by neutralizing IGFBP-5 antibody.

55 By contrast, myoblasts expressing the IGFBP-5 antisense transcript differentiate prematurely a

56 summary, residues 68, 69, 70, 73, and 74 in IGFBP-5 appear to be critical for high affinity binding

57 Therefore, IGFBP-4 and IGFBP-5 appear to be differentially regulated by autocri

58 with two regions of basic amino acids within IGFBP-5 (Arg201-Arg218 and Ala131-Thr141).

59 A library by a yeast two-hybrid system using IGFBP-5 as bait and identified fibronectin (FN) as a pot

60 identify proteins that bind to IGFBP-5 using IGFBP-5 as bait in a yeast two-hybrid screen of a U2 hum

61 in controlling the expression of IGFBP-4 and IGFBP-5 as well as the effects of these IGFBPs in modula

62 nsulin-like growth factor binding protein-5 (IGFBP-5), as it was mimicked by recombinant IGFBP-5 and

63 It was found that IGF binding protein 5 (IGFBP-5), as well as three IGFs expressed in early embry

64 IGFBP-5 augments the effects of IGF-I by facilitating in

65 These results suggest that FN and IGFBP-5 bind to each other, and this binding negatively

66 IGFBP-5 binds to extracellular IGFs and modulates IGF ac

67 s not only establish a disulfide bond map of IGFBP-5 but also define a general approach that takes ad

68 The purified protease cleaved IGFBP-5 but had no activity against IGFBP-1 through -4.

69 F-I, an analogue with decreased affinity for IGFBP-5 but normal affinity for the IGF-I receptor, show

70 revealed that purified FHL2 interacted with IGFBP-5 but not with IGFBP-3, -4, or -6.

71 ed C1s, was shown to inhibit the cleavage of IGFBP-5 by the protease in the conditioned medium.

72 ely regulates the ligand-dependent action of IGFBP-5 by triggering IGFBP-5 proteolysis.

73 ay using deletion mutants indicated that the IGFBP-5 C domain binds to the 10th and 11th type I repea

74 P-5 points mutants, we demonstrated that the IGFBP-5 C-domain is necessary and sufficient for its nuc

75 first demonstration that over-expression of IGFBP-5 can lead to; impaired mammary development, incre

76 IGFBP-5 caused a concentration-dependent increase in [(3

77 ed in pSMC transfected with mutant or native IGFBP-5 cDNAs.

78 tions for residues 68, 69, 70, 73, and 74 in IGFBP-5 (changing one charged residue, Lys(68), to a neu

79 nt to alphaT3-1), with IGF-II levels low and IGFBP-5 concentrated in the anterior pituitary rostral t

80 ysates from U2 cells overexpressing FHL2 and IGFBP-5 confirmed that interaction between IGFBP-5 and F

81 have proposed that the N-terminal region of IGFBP-5 contains a hydrophobic patch between residues 49

82 Because IGFBP-5 contains a nuclear localization sequence that me

83 differentiation by high level expression of IGFBP-5 could be overcome by exogenous IGFs, with des (1

84 In contrast, the same amount of native IGFBP-5 did not inhibit IGF-I actions.

85 gest significant IGF-independent actions for IGFBP-5 during development.

86 we use these cells to study the function of IGFBP-5 during myogenesis, a process stimulated by IGFs.

87 blasts derived from IGF-I knockout mice, the IGFBP-5 effect was studied in the presence of exogenousl

88 endogenous IGFBP-5 or transiently expressed IGFBP-5-EGFP, but not IGFBP-4-EGFP, is localized in the

89 The present study determined whether IGFBP-5 exerts direct effects on growth in human intesti

90 The exact mechanism by which IGFBP-5 exerts these novel fibrotic effects is unknown.

91 sults indicate that endogenous and exogenous IGFBP-5 exhibits opposing biological actions on cell sur

92 , and type IV collagen have major effects on IGFBP-5 expression and on IGF-I-stimulated pSMC response

93 Progesterone (PG) increased IGFBP-5 expression in normal human osteoblasts and incre

94 dded with Des(1-3)IGF-I, the IGF-I-regulated IGFBP-5 expression was negated.

95 m surrounding Rathke's pouch at e10.5, while IGFBP-5 expression was restricted to the adjacent oral e

96 59, however, did not affect IGF-I-stimulated IGFBP-5 expression.

97 hern analyses were used to define trabecular IGFBP-5 expression.

98 y effects of laminin and type IV collagen on IGFBP-5 expression.

99 ell infiltration may be the direct result of IGFBP-5 expression.

100 ately 1000-fold reduction in the affinity of IGFBP-5 for IGF-I.

101 Amino acid sequencing of purified IGFBP-5 fragments suggested Arg138-Arg139 as the primary

102 This suggests that proteolysis can prevent IGFBP-5 from acting as an inhibitor of IGF-I-stimulated

103 The ECM content of IGFBP-5 from cultures expressing the K211N, R214A, R217A

104 first direct evidence to our knowledge that IGFBP-5 functions as a growth factor that stimulates its

105 IGF-I increased IGFBP-5 gene expression 3-fold in the cells plated on fi

106 results suggest that the action of IGF-I on IGFBP-5 gene expression requires the activation of the P

107 naling pathways in mediating IGF-I-regulated IGFBP-5 gene expression.

108 ion, significantly inhibited IGF-I-regulated IGFBP-5 gene expression.

109 These results suggest that PG may stimulate IGFBP-5 gene transcription via a novel mechanism involvi

110 nsulin-like growth factor-binding protein 5 (IGFBP-5) gene in vascular smooth muscle cells is up-regu

111 Here we report that there are 2 igfbp-5 genes in zebrafish and other teleost fish.

112 IGFBP-5 had an inhibitory effect on IGF-I-stimulated DNA

113 evel; overexpression of IGFBP-4 or wild type IGFBP-5 had no such effect.

114 This study provides evidence that IGFBP-5 has an effect on human hair shape, and that lent

115 Because IGFBP-5 has been shown to regulate IGF-I actions, unders

116 IGFBP-5 has been suggested to induce apoptosis by seques

117 nsulin-like growth factor-binding protein-5 (IGFBP-5) has been shown to bind to fibroblast extracellu

118 nsulin-like growth factor-binding protein-5 (IGFBP-5) has IGF-1-independent intranuclear effects that

119 In contrast, IGFBP-5 hybridization occurs over both myometrial layers

120 binding site as detergent and a fragment of IGFBP-5 identified in other IGF-I complexes.

121 ng molecules, such as IGF binding protein-5 (IGFBP-5), IGF-1 receptor (IGF-1R), and phosphoinositide

122 The mRNA expression of IGFBP-5, IGF-1R, and PI3K was constitutively upregulated

123 Knockdown of IGFBP-5 impairs myogenesis and suppresses IGF-II gene ex

124 Egr-1 was up-regulated by IGFBP-5 in a MAPK-dependent manner and bound to nuclear

125 d RNA (siRNA) to trigger RNA interference of IGFBP-5 in human osteosarcoma cells.

126 Furthermore, the role of IGFBP-5 in IGF-1 signaling was verified by annexin-V sta

127 dy the consequence of accumulation of intact IGFBP-5 in medium, we determined the cleavage site in IG

128 eport the nuclear localization of endogenous IGFBP-5 in mouse embryonic skeletal cells.

129 , our results suggest that overexpression of IGFBP-5 in mouse lung results in fibroblast activation,

130 -1 may be facilitated by the upregulation of IGFBP-5 in PDLF.

131 mine the physiological role(s) of endogenous IGFBP-5 in regulating bone cell growth, differentiation,

132 muscle differentiation, and imply a role for IGFBP-5 in regulating IGF action during myogenic develop

133 The findings define a mechanism for cleaving IGFBP-5 in the culture medium, thus allowing release of

134 death we created transgenic mice expressing IGFBP-5 in the mammary gland using a mammary-specific pr

135 sion, the accumulation of protease-resistant IGFBP-5 in the medium was inhibitory to IGF-I actions on

136 Transgenic dams produced IGFBP-5 in their milk at concentrations similar to those

137 The function of IGFBP-5 in these physiological and pathological situatio

138 glutathione S-transferase-IGFBP-5 and native IGFBP-5 in vitro and by co-immunoprecipitation in vivo.

139 Here, we further examined the effect of IGFBP-5 in vivo by intratracheal administration of repli

140 Overexpression of IGF-binding protein 5 (IGFBP-5) in the human hair xenografts obtained from stra

141 ed from IGF-I KO mice with recombinant human IGFBP-5 increased both proliferation and alkaline phosph

142 s added in excess, suggesting that exogenous IGFBP-5 increases apoptosis by binding to and inhibiting

143 In addition, exogenous IGFBP-5 induced alpha-smooth muscle actin expression in

144 Moreover, IGFBP-5 induced cell migration in an Egr-1-dependent man

145 ls of mice treated with Ad5, suggesting that IGFBP-5 induced epithelial-mesenchymal transition.

146 Addition of IGFBP-4 blocked IGF-I- but not IGFBP-5-induced cell proliferation in osteoblasts derive

147 examined the signaling cascades that mediate IGFBP-5-induced fibrosis.

148 Thus, the IGFBP-5-induced fibrotic phenotype in vivo may represent

149 The magnitudes of IGFBP-5-induced increases in ALP and osteocalcin in pari

150 IGFBP-5-induced phosphorylation of p38 MAP kinase, which

151 Taken together, our findings suggest that IGFBP-5 induces a fibrotic phenotype via the activation

152 These data indicate that IGFBP-5 induces formation of a FLNa-based nuclear shuttl

153 Treatment of cells with IGFBP-5 induces migration, prevents apoptosis, and leads

154 We demonstrate for the first time that IGFBP-5 induction of extracellular matrix occurs indepen

155 d identified fibronectin (FN) as a potential IGFBP-5-interacting partner.

156 of IGFBP-5 into the nucleus, we propose that IGFBP-5 interacts with nuclear proteins to affect transc

157 munoprecipitation experiments indicated that IGFBP-5 interacts with the nuclear histone-DNA complex.

158 lization sequence that mediates transport of IGFBP-5 into the nucleus, we propose that IGFBP-5 intera

159 Our findings suggest that IGFBP-5 is a direct or indirect target for Stat3 and its

160 IGFBP-5 is also found in the nuclei of cultured cells an

161 IGFBP-5 is also found in the nucleus of mammalian cells

162 However, IGFBP-5 is also secreted into conditioned medium of cult

163 ive to IGF-I, suggesting that ECM binding of IGFBP-5 is an important variable that determines cellula

164 en added exogenously, (125)I- or Cy3-labeled IGFBP-5 is capable of cellular entry and nuclear translo

165 nuclear localization, suggesting the nuclear IGFBP-5 is derived from the secreted protein.

166 IGFBP-5 is induced before the elevation of IGF-II expres

167 These results suggest that IGFBP-5 is localized in VSMC nucleus and possesses trans

168 ntriguingly, the transactivation activity of IGFBP-5 is masked by negative regulatory elements locate

169 IGFBP-5 is synthesized by pSMC and binds to the extracel

170 IGFBP-5 is the most conserved IGFBP, and contains 18 cys

171 IGFBP-5 is the most conserved of these and is up-regulat

172 owever, Northern blot analysis suggests that IGFBP-5 is the predominant binding protein produced.

173 In this cell type, the biosynthesis of IGFBP-5 is up-regulated by IGF-I.

174 nsulin-like growth factor-binding protein 5 (IGFBP-5) is a secreted protein that binds to insulin-lik

175 nsulin-like growth factor-binding protein-5 (IGFBP-5) is abundantly expressed in bone cells.

176 like growth factor (IGF) binding protein- 5 (IGFBP-5) is overexpressed in lung fibrosis and induces t

177 nsulin-like growth factor-binding protein-5 (IGFBP-5) is produced by osteoblasts and potentiates insu

178 n of a siRNA-resistant IGFBP-5 mutant in the IGFBP-5 knock-down cells restored the levels of survival

179 exogenous IGFBP-5 not only failed to rescue IGFBP-5 knock-down-induced apoptosis, it caused a furthe

180 or constitutively activating Akt rescues the IGFBP-5 knockdown-caused defects.

181 Extracellular matrix binding of IGFBP-5 leads to a decrease in its affinity for insulin-

182 ease in concentrations of intact IGFBP-3 and IGFBP-5 leads to an increase in IGF-1 which is associate

183 In this report, we show that IGFBP-5 leads to dephosphorylation of FLNa with subseque

184 mary fibroblasts in a time-dependent manner, IGFBP-5 levels were not increased by transforming growth

185 ly associated with a significant increase in IGFBP-5 levels.

186 In contrast to IGFBP-5, local administration of IGFBP-4 had no signific

187 ssion and regulation of its accessibility by IGFBP-5 may play a role in anterior pituitary differenti

188 FLNa knockdown prevents IGFBP-5-mediated increases in lamc1 transcription.

189 IGFBP-5 mediates its profibrotic effects through fibrobl

190 IGFBP-5 message was detected in all samples, but was lea

191 , targeting against a sequence unique to the IGFBP-5 middle domain, efficiently reduced IGFBP-5 mRNA

192 ained abundant fibronectin and had increased IGFBP-5 mRNA (4.5 +/- 1.5-fold) compared with tissue fro

193 GF-I antibody to determine if it would alter IGFBP-5 mRNA abundance.

194 e IGFBP-5 middle domain, efficiently reduced IGFBP-5 mRNA and protein levels.

195 udy we demonstrate that porcine SMCs express IGFBP-5 mRNA and synthesize and secrete the protein.

196 This culture density-dependent change in IGFBP-5 mRNA correlated closely with endogenous IGF-I le

197 hat had been plated on fibronectin inhibited IGFBP-5 mRNA expression.

198 IGFBP-5 mRNA in sparse cultures was 3-fold higher compar

199 tment of VSMC with exogenous IGF-I increased IGFBP-5 mRNA levels, we neutralized the effect of endoge

200 This resulted in a 4.4-fold decrease in IGFBP-5 mRNA levels.

201 enzimidazole demonstrated that PGE2 enhanced IGFBP-5 mRNA stability by 2-fold, increasing the t1/2 fr

202 Stac3, which results in increased levels of Igfbp-5 mRNA, did not lead to increased differentiation.

203 Expression of IGF-II and IGFBP-5 mRNAs was both temporally and spatially regulate

204 By using a non-IGF-binding IGFBP-5 mutant and an IGF-I-neutralizing antibody, it wa

205 An IGFBP-5 mutant containing alterations of basic residues

206 rentiation, whereas an IGF binding-deficient IGFBP-5 mutant has no effect.

207 Overexpression of a siRNA-resistant IGFBP-5 mutant in the IGFBP-5 knock-down cells restored

208 folding induced by mutagenesis, because the IGFBP-5 mutant was fully susceptible to proteolytic clea

209 Further motif analysis revealed that the IGFBP-5 N-domain contains a putative transactivation dom

210 to GAL-4 DNA dinging domain and tested, the IGFBP-5 N-domain has strong transactivation activity.

211 analysis revealed several amino acids in the IGFBP-5 N-domain that are not present in IGFBP-1.

212 there are several conserved residues in the IGFBP-5 N-terminal region that are critical for transact

213 lic proteins that are known to interact with IGFBP-5, no known transcription factors were found.

214 Our observations also suggest that IGFBP-5 normally inhibits muscle differentiation, and im

215 PCR, using a variety of specific primers for IGFBP-5, Northern analysis, Western immunoblots, and imm

216 Paradoxically, the addition of exogenous IGFBP-5 not only failed to rescue IGFBP-5 knock-down-ind

217 IGFBP-5 not only modulates IGF-I actions, but it also st

218 y, inhibition of protein secretion abolishes IGFBP-5 nuclear localization, suggesting the nuclear IGF

219 we evaluated in vitro and in vivo effects of IGFBP-5 on bone formation parameters using the IGF-I kno

220 We examined the effects of IGFBP-5 on early growth response (Egr)-1, a transcriptio

221 he FN-null cells, the potentiating effect of IGFBP-5 on IGF-I-induced cell migration was abolished.

222 IGFBP-5, on the other hand, potentiated the effect of IG

223 In this study, we show that endogenous IGFBP-5 or transiently expressed IGFBP-5-EGFP, but not I

224 d collagen bundle thickness were observed in IGFBP-5-overexpressing mice.

225 e fibroblasts were detected in the dermis of IGFBP-5-overexpressing mouse skin.

226 IGF-II in type 2 receptor-null mice; mutant IGFBP-5 overexpression could not.

227 sing dorsoventral (IGF-II) and ventrodorsal (IGFBP-5) patterns, with IGF-II excluded from the rostral

228 Using a series of IGFBP-4/5 chimeras and IGFBP-5 points mutants, we demonstrated that the IGFBP-5

229 IGFBP-5 potentiated IGF-I-induced cell migration in FN-n

230 cient to overcome the high concentrations of IGFBP-5 produced by these transgenic animals.

231 We have previously demonstrated that IGFBP-5 production by mammary epithelial cells increases

232 In osteoblasts, IGFBP-5 production is stimulated by prostaglandin E2 (PG

233 structs indicates that PG transactivation of IGFBP-5 promoter activity does not require the PG respon

234 uct containing base pairs -252 to +24 of the IGFBP-5 promoter, we found that both PR(A) and PR(B) iso

235 ated at positions -44 to -36 in the proximal IGFBP-5 promoter.

236 These findings suggest that IGFBP-5 promotes muscle cell differentiation by binding

237 stigate whether local IGF binding protein-5 (IGFBP-5) promotes the myogenic action of IGF-II.

238 Direct analysis of IGFBP-3 and IGFBP-5 protease activity showed that IGFBP-5 was degrad

239 ptible to proteolytic cleavage by a specific IGFBP-5 protease.

240 Inhibition of IGFBP-5 proteolysis restored the potentiating effect of

241 nd-dependent action of IGFBP-5 by triggering IGFBP-5 proteolysis.

242 Overexpression of IGFBP-5 provides a novel model for studying the pathogen

243 Therefore, wild-type IGFBP-5 provides a very effective mechanism for the inhi

244 rase reporter construct containing the human IGFBP-5 proximal promoter sequence, which includes TATA

245 f IGF-I, presumably by activating a distinct IGFBP-5 receptor serine kinase.

246 Mutation of the heparin-binding motif of IGFBP-5 reduced its migration promoting activity.

247 This mutant IGFBP-5 remained intact even after 24 h of incubation an

248 Further, overexpression of wild-type IGFBP-5 rescued the lethal phenotype induced by "excess"

249 hen added with low concentrations of IGF-II, IGFBP-5 restores IGF-II expression and myogenic differen

250 Knock-down of IGFBP-5 resulted in a significant increase in the number

251 genous IGF-I stimulates growth and increases IGFBP-5 secretion.

252 ical situations is unclear, however, several IGFBP-5 sequence motifs and studies in vitro suggest IGF

253 Even though wild-type IGFBP-5 severely disrupted the IGF axis, we found no evi

254 The IGFBP-5 siRNA did not change the levels of IGFBP-4, a st

255 The IGFBP-5 siRNA, targeting against a sequence unique to th

256 IGFBP-5-stimulated [(3)H]thymidine incorporation and IGF

257 These data show that IGFBP-5 stimulates growth and IGF-I secretion in human i

258 t in osteoblasts and kidney mesangial cells, IGFBP-5 stimulates proliferation and filopodia formation

259 port the concept that IGF-binding protein-5 (IGFBP-5) stimulates bone formation, at least in part, vi

260 ption factors and regulates transcription of IGFBP-5 target genes.

261 ctin, they synthesized 6.0 +/- 1.2-fold more IGFBP-5 than did cells maintained on laminin and type IV

262 When the amount of IGFBP-5 that is bound to ECM is increased by exogenous a

263 we identified the specific basic residues in IGFBP-5 that mediate its binding to porcine smooth-muscl

264 ic changes in IGFBP expression profile, with IGFBP-5 the predominant binding protein produced by myof

265 In the presence of exogenous IGFBP-5, the annexin-V-positive cells were significantly

266 IGFBP-5, the most conserved of six IGFBPs characterized

267 P1 isoform that has been reported to process IGFBP-5, thereby playing a critical role in insulin grow

268 GFBP-5 to FN had no effect on the ability of IGFBP-5 to bind IGF-I, but it increased the proteolytic

269 The addition of IGFBP-5 to cultures plated on laminin and type IV collag

270 Binding of IGFBP-5 to FN had no effect on the ability of IGFBP-5 to

271 Likewise, the ability of IGFBP-5 to inhibit IGF-I-stimulated receptor phosphoryla

272 positions 207 and 214 mediate the binding of IGFBP-5 to pSMC/ECM.

273 ling, which facilitates the translocation of IGFBP-5 to the nucleus.

274 n vitro results, a single local injection of IGFBP-5 to the outer periosteum of the parietal bone of

275 on in normal human osteoblasts and increased IGFBP-5 transcription in U2 human osteosarcoma cells.

276 IGFBP-5 transcripts also increased after adenoviral gene

277 ok studies to identify proteins that bind to IGFBP-5 using IGFBP-5 as bait in a yeast two-hybrid scre

278 This pro-apoptotic action of exogenous IGFBP-5 was abolished when IGF-I was added in excess, su

279 1 knockout mice, induction of fibronectin by IGFBP-5 was abolished.

280 However, IGFBP-5 was also present at low levels in the ciliary bo

281 re medium of transfected cells, while native IGFBP-5 was degraded into fragments, PSMC overexpressing

282 -3 and IGFBP-5 protease activity showed that IGFBP-5 was degraded more rapidly and that PB-145 and PP

283 Trabecular IGFBP-5 was distributed throughout the meshwork in the e

284 As glia-derived IGFBP-5 was earlier found to promote photoreceptor survi

285 Nuclear localization of both FHL2 and IGFBP-5 was evident from Western immunoblot analysis and

286 immunohistochemical analysis, confirmed that IGFBP-5 was expressed in the TM.

287 inhibitory effects of the protease resistant IGFBP-5 was further demonstrated in pSMC transfected wit

288 This effect of IGFBP-5 was inhibited by soluble heparin and by treating

289 In contrast, the synthesis of IGFBP-5 was inversely correlated with culture density, a

290 etion mutants, the transactivation domain of IGFBP-5 was mapped to its N-terminal region.

291 nsulin-like growth factor binding protein 5 (IGFBP-5) was observed in vitro, and its differential dis

292 e growth factor signaling system, IGF-II and IGFBP-5, was found in the alphaT1-1 precursor cell line,

293 nsulin-like growth factor binding protein 5 (IGFBP-5), we undertook to determine whether inhibiting C

294 echanisms governing these diverse actions of IGFBP-5, we screened a human cDNA library by a yeast two

295 Notably, Egr-1 levels, similar to IGFBP-5, were increased in vivo in lung tissues and in v

296 nsulin-like growth factor-binding protein-5 (IGFBP-5), which could contribute to its anti-apoptotic e

297 were introduced to create protease-resistant IGFBP-5, which has the same affinity for IGF-I as the na

298 nsulin-like growth factor binding protein-5 (IGFBP-5) while screening for uniquely expressed trabecul

299 found no evidence for interaction of mutant IGFBP-5 with the IGF system.

300 s with silver staining showed two bands, and IGFBP-5 zymography showed a single 88-kDa band.