Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): Characterization of connective tissue growth factor as a member of the IGFBP superfamily
Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): Characterization of connective tissue growth factor as a member of the IGFBP superfamily
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DOI：
10.1073/pnas.94.24.12981
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发表时间：
1997-11-25
影响因子：
11.1
通讯作者：
Rosenfeld, RG
中科院分区：
文献类型：
--
作者：
Kim, HS;Nagalla, SR;Rosenfeld, RG
胰岛素样生长因子（IGF）结合蛋白（IGFBP）调节胰岛素样生长因子在内分泌、旁分泌和自分泌环境中的作用。此外，一些IGFBP似乎表现出不依赖IGF的生物学效应。迄今为止已经表征的六种高亲和力IGFBP总体上表现出40-60%的氨基酸序列同一性，在其NH 2和COOH末端具有最保守的序列。我们最近证明了mac 25/IGFBP-7基因的产物，其在NH 2末端显示出显著的保守性，包括“IGFBP基序”，密切相关的哺乳动物基因结缔组织生长因子（CTGF）基因、nov和IGFBP 61编码分泌蛋白，所述分泌蛋白在其NH 2末端也含有保守序列和IGFBP基序，为了确定这些基因是否与mac 25/IGFBP-7一起沿着编码低亲和力IGFBP家族，我们评估了重组人CTGF（rhCTGF）的IGF结合特性。通过使用I-125标记的IGF-I或IGF-II和未标记的IGF的Western配体印迹、亲和交联和竞争性亲和结合测定来证明杆状病毒合成的rhCTGF结合IGF的能力。CTGF与mac 25/IGFBP-7一样，特异性结合IGF，尽管亲和力相对较低。基于这些数据，我们提出CTGF代表IGFBP家族的另一个成员（IGFBP-8），并且CTGF基因mac 25/IGFBP-7、nov和p161是低亲和力IGFBP基因家族的成员。这些基因，沿着那些编码高亲和力IGFBP 1-6的基因，共同构成IGFBP超家族，其产物以IGF依赖性或IGF非依赖性模式发挥功能以调节正常和肿瘤细胞生长。
The insulin-like growth factor (IGF) binding proteins (IGFBPs) modulate the actions of the insulin-like growth factors in endocrine, paracrine, and autocrine settings, Additionally, some IGFBPs appear to exhibit biological effects that are IGF independent, The six high-affinity IGFBPs that have been characterized to date exhibit 40-60% amino acid sequence identity overall, with the most conserved sequences in their NH2 and COOH termini. We have recently demonstrated that the product of the mac25/IGFBP-7 gene, which shows significant conservation in the NH2 terminus, including an ''IGFBP motif'' (GCGCCXXC), exhibits low-affinity IGF binding, The closely related mammalian genes connective tissue growth factor (CTGF) gene, nov, and cyr61 encode secreted proteins that also contain the conserved sequences and IGFBP motifs in their NH2 termini, To ascertain if these genes, along with mac25/IGFBP-7, encode a family of low-affinity IGFBPs, we assessed the IGF binding characteristics of recombinant human CTGF (rhCTGF), The ability of baculovirus-synthesized rhCTGF to bind IGFs was demonstrated by Western ligand blotting, affinity crosslinking, and competitive affinity binding assays using I-125-labeled IGF-I or IGF-II and unlabeled IGFs. CTGF, like mac25/IGFBP-7, specifically binds IGFs, although with relatively low affinity. On the basis of these data, we propose that CTGF represents another member of the IGFBP family (IGFBP-8) and that the CTGF gene, mac25/IGFBP-7, nov, and cyr61 are members of a family of low-affinity IGFBP genes, These genes, along with those encoding the high-affinity IGFBPs 1-6, together constitute an IGFBP superfamily whose products function in IGF-dependent or IGF-independent modes to regulate normal and neoplastic cell growth.