The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix.
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.
Gregory
Kate E
KE
Shriners Hospital for Children, Portland, Oregon 97239, USA.
Ono
Robert N
RN
Charbonneau
Noe L
NL
Kuo
Chiu-Liang
CL
Keene
Douglas R
DR
Bächinger
Hans Peter
HP
Sakai
Lynn Y
LY
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000737:chemistry* / Q000502:physiology; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism*; D000071838:Fibrillin-1; D000071837:Fibrillins; D005960:Glucosides / Q000494:pharmacology; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000196:embryology; D053779:Latent TGF-beta Binding Proteins; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D012542:Scattering, Radiation; D016626:Shadowing Technique, Histology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D014466:Ultraviolet Rays; D054392:Adipokines
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D018076:DNA, Complementary; D000071838:Fibrillin-1; D000071837:Fibrillins; D005960:Glucosides; D006639:Histidine; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C525819:BMP7 protein, human; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse; C509032:LTBP1 protein, human; C509033:Ltbp1 protein, mouse; C018619:octyl-beta-D-glucoside