The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix
The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix
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DOI：
10.1074/jbc.m504270200
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发表时间：
2005-07-29
影响因子：
4.8
通讯作者：
Sakai, LY
中科院分区：
文献类型：
--
作者：
Gregory, KE;Ono, RN;Sakai, LY
生化和生物物理方法表明，BMP-7是一种稳定的复合体，由经过处理的生长因子二聚体与其两个前域前肽链非共价结合而成，并且BMP-7复合体的结构类似于小的转化生长因子-β(TGF-β)复合体。由于转化生长因子β的前域与潜在的转化生长因子β结合蛋白(一类与纤维蛋白同源的分子)相互作用，BMP-7的前域被测试与纤维蛋白-1或LTBP-1的结合。BMP-7前结构域和BMP-7复合体，而不是分离的生长因子二聚体，与纤维蛋白-1的N-末端区域相互作用。这种相互作用可能针对细胞外基质中的BMP-7复合体和纤维素微纤维。BMP-7在肾被膜和皮肤等组织中的免疫定位显示与纤维蛋白的共同定位。然而，BMP-7在其他已知为BMP-7信号活性部位的组织中的免疫定位并不明显，这表明BMP-7在某些组织中的免疫定位代表特定的细胞外存储部位。这些研究表明，转化生长因子β样生长因子的前体对于细胞外基质中生长因子的定位和浓缩是重要的。此外，它们增加了其他转化生长因子β样生长因子的前体与纤维蛋白和/或LTBP相互作用的可能性，并且也针对细胞外基质。
Biochemical and biophysical methods are used to show that BMP-7 is secreted as a stable complex consisting of the processed growth factor dimer noncovalently associated with its two prodomain propeptide chains and that the BMP-7 complex is structurally similar to the small transforming growth factor beta (TGF beta) complex. Because the prodomain of TGF beta interacts with latent TGF beta-binding proteins, a family of molecules homologous to the fibrillins, the prodomain of BMP-7 was tested for binding to fibrillin-1 or to LTBP-1. The BMP-7 prodomain and BMP-7 complex, but not the separated growth factor dimer, interact with N-terminal regions of fibrillin-1. This interaction may target the BMP-7 complex to fibrillin microfibrils in the extracellular matrix. Immunolocalization of BMP-7 in tissues like the kidney capsule and skin reveals co-localization with fibrillin. However, BMP-7 immunolocalization in other tissues known to be active sites for BMP-7 signaling is not apparent, suggesting that immunolocalization of BMP-7 in certain tissues represents specific extracellular storage sites. These studies suggest that the prodomains of TGF beta-like growth factors are important for positioning and concentrating growth factors in the extracellular matrix. In addition, they raise the possibility that prodomains of other TGF beta-like growth factors interact with fibrillins and/or LTBPs and are also targeted to the extracellular matrix.