Leal S M, Liu Q, Huang S S, Huang J S
Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA.
J Biol Chem. 1997 Aug 15;272(33):20572-6. doi: 10.1074/jbc.272.33.20572.
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 125I-transforming growth factor (TGF)-beta1 binding to the type V TGF-beta receptor (Mr 400,000) in mink lung epithelial cells. We also demonstrate that the approximately 400-kDa 125I-IGFBP-3 affinity-labeled putative IGFBP-3 receptor is immunoprecipitated by specific antiserum to the type V TGF-beta receptor. The 125I-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-beta1 peptide antagonist. The 125I-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.
胰岛素样生长因子结合蛋白3（IGFBP - 3）已被证明可通过依赖胰岛素样生长因子（IGF）和不依赖IGF的机制抑制细胞生长。介导不依赖IGF的生长抑制作用的假定细胞表面IGFBP - 3受体尚未得到鉴定。在此我们表明，重组人IGFBP - 3可抑制125I转化生长因子（TGF）-β1与水貂肺上皮细胞中的V型TGF - β受体（分子量400,000）结合。我们还证明，针对V型TGF - β受体的特异性抗血清可免疫沉淀约400 kDa的125I - IGFBP - 3亲和标记的假定IGFBP - 3受体。在这些细胞中，由DNA合成测量的假定受体的125I - IGFBP - 3亲和标记和IGFBP - 3诱导的生长抑制被一种TGF - β1肽拮抗剂所阻断。125I - IGFBP - 3亲和标记的假定受体仅能在表达V型TGF - β受体的细胞中检测到，而在缺乏V型TGF - β受体的细胞中则检测不到。这些结果表明，V型TGF - β受体是假定的IGFBP - 3受体，并且IGFBP - 3是V型TGF - β受体的功能性配体。
