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 beta (TGFbeta) complex. Because the prodomain of TGFbeta interacts with latent TGFbeta-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 TGFbeta-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 TGFbeta-like growth factors interact with fibrillins and/or LTBPs and are also targeted to the extracellular matrix.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Bone Morphogenetic Protein 7
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Bone Morphogenetic Proteins / chemistry*
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Bone Morphogenetic Proteins / physiology
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Cell Line
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DNA, Complementary / metabolism
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Dimerization
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Enzyme-Linked Immunosorbent Assay
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Extracellular Matrix / metabolism*
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Fibrillin-1
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Fibrillins
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Glucosides / pharmacology
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Histidine / chemistry
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Humans
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Hydrogen-Ion Concentration
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Intracellular Signaling Peptides and Proteins / metabolism
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Kidney / embryology
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Latent TGF-beta Binding Proteins
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Light
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Mice
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Mice, Inbred BALB C
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Microfilament Proteins / chemistry
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Microfilament Proteins / metabolism
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Microscopy, Electron
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Microscopy, Fluorescence
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Molecular Sequence Data
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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Scattering, Radiation
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Shadowing Technique, Histology
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Signal Transduction
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Transforming Growth Factor beta / chemistry*
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Transforming Growth Factor beta / metabolism
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Transforming Growth Factor beta / physiology
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Ultraviolet Rays
Substances
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BMP7 protein, human
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Bone Morphogenetic Protein 7
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Bone Morphogenetic Proteins
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DNA, Complementary
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FBN1 protein, human
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Fbn1 protein, mouse
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Fibrillin-1
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Fibrillins
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Glucosides
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Intracellular Signaling Peptides and Proteins
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LTBP1 protein, human
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Latent TGF-beta Binding Proteins
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Ltbp1 protein, mouse
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Microfilament Proteins
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Recombinant Proteins
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Transforming Growth Factor beta
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octyl-beta-D-glucoside
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Histidine