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 Sakai

Research output: Contribution to journalArticle

136 Citations (Scopus)

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

Fingerprint

Bone Morphogenetic Protein 7
Extracellular Matrix
Transforming Growth Factors
Intercellular Signaling Peptides and Proteins
Tissue
Dimers
Microfibrils
Capsules
Catalytic Domain
Skin
Carrier Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Gregory, K. E., Ono, R. N., Charbonneau, N. L., Kuo, C. L., Keene, D. R., Bächingeri, H. P., & Sakai, L. (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

The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix. / Gregory, Kate E.; Ono, Robert N.; Charbonneau, Noe L.; Kuo, Chiu Liang; Keene, Douglas R.; Bächingeri, Hans Peter; Sakai, Lynn.

In: Journal of Biological Chemistry, Vol. 280, No. 30, 29.07.2005, p. 27970-27980.

Research output: Contribution to journalArticle

Gregory, KE, Ono, RN, Charbonneau, NL, Kuo, CL, Keene, DR, Bächingeri, HP & Sakai, L 2005, 'The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix', Journal of Biological Chemistry, vol. 280, no. 30, pp. 27970-27980. https://doi.org/10.1074/jbc.M504270200
Gregory KE, Ono RN, Charbonneau NL, Kuo CL, Keene DR, Bächingeri HP et al. The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix. Journal of Biological Chemistry. 2005 Jul 29;280(30):27970-27980. https://doi.org/10.1074/jbc.M504270200
Gregory, Kate E. ; Ono, Robert N. ; Charbonneau, Noe L. ; Kuo, Chiu Liang ; Keene, Douglas R. ; Bächingeri, Hans Peter ; Sakai, Lynn. / The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 30. pp. 27970-27980.
@article{094672b7280c406b858e79bb6fd15d76,
title = "The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix",
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.",
author = "Gregory, {Kate E.} and Ono, {Robert N.} and Charbonneau, {Noe L.} and Kuo, {Chiu Liang} and Keene, {Douglas R.} and B{\"a}chingeri, {Hans Peter} and Lynn Sakai",
year = "2005",
month = "7",
day = "29",
doi = "10.1074/jbc.M504270200",
language = "English (US)",
volume = "280",
pages = "27970--27980",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "30",

}

TY - JOUR

T1 - The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix

AU - Gregory, Kate E.

AU - Ono, Robert N.

AU - Charbonneau, Noe L.

AU - Kuo, Chiu Liang

AU - Keene, Douglas R.

AU - Bächingeri, Hans Peter

AU - Sakai, Lynn

PY - 2005/7/29

Y1 - 2005/7/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=23044515502&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23044515502&partnerID=8YFLogxK

U2 - 10.1074/jbc.M504270200

DO - 10.1074/jbc.M504270200

M3 - Article

C2 - 15929982

AN - SCOPUS:23044515502

VL - 280

SP - 27970

EP - 27980

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 30

ER -