The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix

Kate E. Gregory, Robert N. Ono, Noe L. Charbonneau, Chiu Liang Kuo, Douglas R. Keene, Hans Peter Bächingeri, Lynn Y. Sakai

Research output: Contribution to journalArticle

141 Scopus citations

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 languageEnglish (US)
Pages (from-to)27970-27980
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number30
DOIs
StatePublished - Jul 29 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Gregory, K. E., Ono, R. N., Charbonneau, N. L., Kuo, C. L., Keene, D. R., Bächingeri, H. P., & Sakai, L. Y. (2005). The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix. Journal of Biological Chemistry, 280(30), 27970-27980. https://doi.org/10.1074/jbc.M504270200