The type V transforming growth factor beta receptor is the putative insulin-like growth factor-binding protein 3 receptor

The type V transforming growth factor beta receptor is the putative insulin-like growth factor-binding protein 3 receptor
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DOI:
10.1074/jbc.272.33.20572
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发表时间:
1997-08-15
影响因子:
4.8
通讯作者:
Huang, JS
Huang, JS
中科院分区:
生物学2区
文献类型:
--
作者:
Leal, SM;Liu, QJ;Huang, JS

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胰岛素样生长因子结合蛋白3(IGFBP-3)通过胰岛素样生长因子依赖性和非依赖性机制抑制细胞生长,介导胰岛素样生长因子非依赖性生长抑制的假定细胞表面IGFBP-3受体尚未被鉴定,我们发现重组人IGFBP-3抑制I-125转化生长因子(TGF)-β 1与V型TGF-β受体的结合(M-r 400,000)在水貂肺上皮细胞中,我们还证明,与400-kDa I-125-IGFBP-3亲和力标记的推定IGFBP-3受体类似,V型TGF-β受体的特异性抗血清可免疫沉淀,I-125-IGFBP-3亲和标记的推定受体和IGFBP-3-通过这些细胞中的DNA合成测量的诱导的生长抑制被TGF-β(1)肽拮抗剂阻断,I-125-IGFBP-3亲和标记的推定受体只能在表达V型TGF-β受体的细胞中检测到,这些结果表明,V型TGF-β受体是推定的IGFBP-3受体,IGFBP-3是V型TGF-β受体的功能性配体。
Insulin-like growth factor-binding protein 3 (IGFBP-3) has been shown to inhibit cell growth by IGF-dependent and -independent mechanisms, The putative cell-surface IGFBP-3 receptor that mediates the IGF-independent growth inhibition has not been identified, Here we show that recombinant human IGFBP-3 inhibits I-125-transforming growth factor (TGF)-beta(1) binding to the type V TGF-beta receptor (M-r 400,000) in mink lung epithelial cells, We also demonstrate that the similar to 400-kDa I-125-IGFBP-3 affinity-labeled putative IGFBP-3 receptor is immunoprecipitated by specific antiserum to the type V TGF-beta receptor, The I-125-IGFBP-3 affinity labeling of the putative receptor and IGFBP-3-induced growth inhibition as measured by DNA synthesis in these cells is blocked by a TGF-beta(1) peptide antagonist, The I-125-IGFBP-3 affinity-labeled putative receptor can only be detected in cells expressing the type V TGF-beta receptor, but not in cells lacking the type V TGF-beta receptor, These results indicate that the type V TGF-beta receptor is the putative IGFBP-3 receptor and that IGFBP-3 is a functional ligand for the type V TGF-beta receptor.