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Enhanced Activity of Transforming Growth Factor beta 1 (TGF-beta 1) Bound to Cartilage Oligomeric Matrix Protein

Haudenschild, Dominik R.; Hong, Eunmee; Yik, Jasper H. N.; Chromy, Brett; Mörgelin, Matthias LU ; Snow, Kaylene D.; Acharya, Chitrangada; Takada, Yoshikazu and Di Cesare, Paul E. (2011) In Journal of Biological Chemistry 286(50). p.43250-43258
Abstract
Cartilage oligomeric matrix protein (COMP) is an important non-collagenous cartilage protein that is essential for the structural integrity of the cartilage extracellular matrix. The repeated modular structure of COMP allows it to "bridge" and assemble multiple cartilage extracellular matrix components such as collagens, matrilins, and proteoglycans. With its modular structure, COMP also has the potential to act as a scaffold for growth factors, thereby affecting how and when the growth factors are presented to cell-surface receptors. However, it is not known whether COMP binds growth factors. We studied the binding interaction between COMP and TGF-beta 1 in vitro and determined the effect of COMP on TGF-beta 1-induced signal transduction... (More)
Cartilage oligomeric matrix protein (COMP) is an important non-collagenous cartilage protein that is essential for the structural integrity of the cartilage extracellular matrix. The repeated modular structure of COMP allows it to "bridge" and assemble multiple cartilage extracellular matrix components such as collagens, matrilins, and proteoglycans. With its modular structure, COMP also has the potential to act as a scaffold for growth factors, thereby affecting how and when the growth factors are presented to cell-surface receptors. However, it is not known whether COMP binds growth factors. We studied the binding interaction between COMP and TGF-beta 1 in vitro and determined the effect of COMP on TGF-beta 1-induced signal transduction in reporter cell lines and primary cells. Our results demonstrate that mature COMP protein binds to multiple TGF-beta 1 molecules and that the peak binding occurs at slightly acidic pH. These interactions were confirmed by dual polarization interferometry and visualized by rotary shadow electron microscopy. There is cation-independent binding of TGF-beta 1 to the C-terminal domain of COMP. In the presence of manganese, an additional TGF-beta-binding site is present in the TSP3 repeats of COMP. Finally, we show that COMP-bound TGF-beta 1 causes increased TGF-beta 1-dependent transcription. We conclude that TGF-beta 1 binds to COMP and that TGF-beta 1 bound to COMP has enhanced bioactivity. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
286
issue
50
pages
43250 - 43258
publisher
ASBMB
external identifiers
  • wos:000298351300045
  • scopus:83355174072
ISSN
1083-351X
DOI
10.1074/jbc.M111.234716
language
English
LU publication?
yes
id
6bb33b27-5d19-45b8-9e00-c13bfb2e9257 (old id 2348321)
date added to LUP
2012-03-01 11:20:06
date last changed
2017-10-01 03:25:17
@article{6bb33b27-5d19-45b8-9e00-c13bfb2e9257,
  abstract     = {Cartilage oligomeric matrix protein (COMP) is an important non-collagenous cartilage protein that is essential for the structural integrity of the cartilage extracellular matrix. The repeated modular structure of COMP allows it to "bridge" and assemble multiple cartilage extracellular matrix components such as collagens, matrilins, and proteoglycans. With its modular structure, COMP also has the potential to act as a scaffold for growth factors, thereby affecting how and when the growth factors are presented to cell-surface receptors. However, it is not known whether COMP binds growth factors. We studied the binding interaction between COMP and TGF-beta 1 in vitro and determined the effect of COMP on TGF-beta 1-induced signal transduction in reporter cell lines and primary cells. Our results demonstrate that mature COMP protein binds to multiple TGF-beta 1 molecules and that the peak binding occurs at slightly acidic pH. These interactions were confirmed by dual polarization interferometry and visualized by rotary shadow electron microscopy. There is cation-independent binding of TGF-beta 1 to the C-terminal domain of COMP. In the presence of manganese, an additional TGF-beta-binding site is present in the TSP3 repeats of COMP. Finally, we show that COMP-bound TGF-beta 1 causes increased TGF-beta 1-dependent transcription. We conclude that TGF-beta 1 binds to COMP and that TGF-beta 1 bound to COMP has enhanced bioactivity.},
  author       = {Haudenschild, Dominik R. and Hong, Eunmee and Yik, Jasper H. N. and Chromy, Brett and Mörgelin, Matthias and Snow, Kaylene D. and Acharya, Chitrangada and Takada, Yoshikazu and Di Cesare, Paul E.},
  issn         = {1083-351X},
  language     = {eng},
  number       = {50},
  pages        = {43250--43258},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Enhanced Activity of Transforming Growth Factor beta 1 (TGF-beta 1) Bound to Cartilage Oligomeric Matrix Protein},
  url          = {http://dx.doi.org/10.1074/jbc.M111.234716},
  volume       = {286},
  year         = {2011},
}