Enhanced Activity of Transforming Growth Factor beta 1 (TGF-beta 1) Bound to Cartilage Oligomeric Matrix Protein
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2348321
- author
- 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.
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 286
- issue
- 50
- pages
- 43250 - 43258
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000298351300045
- scopus:83355174072
- pmid:21940632
- 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
- 2016-04-01 10:52:34
- date last changed
- 2022-01-26 03:17:57
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M111.234716}},
volume = {{286}},
year = {{2011}},
}