Abstract
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 β (TGFβ) complex. Because the prodomain of TGFβ interacts with latent TGFβ-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 TGFβ-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 TGFβ-like growth factors interact with fibrillins and/or LTBPs and are also targeted to the extracellular matrix.
Original language | English (US) |
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Pages (from-to) | 27970-27980 |
Number of pages | 11 |
Journal | Journal of Biological Chemistry |
Volume | 280 |
Issue number | 30 |
DOIs | |
State | Published - Jul 29 2005 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology