Enhanced activity of transforming growth factor β1 (TGF-β1) bound to cartilage oligomeric matrix protein

Dominik R. Haudenschild, Eunmee Hong, Jasper H N Yik, Brett Chromy, Matthias Mörgelin, Kaylene D. Snow, Chitrangada Acharya, Yoshikazu Takada, Paul E. Di Cesare

研究成果: 雜誌貢獻文章

36 引文 斯高帕斯(Scopus)

摘要

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-β1 in vitro and determined the effect ofCOMPon TGF-β1-induced signal transduction in reporter cell lines and primary cells. Our results demonstrate that mature COMP protein binds to multiple TGF-β1 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-β1 to the C-terminal domain of COMP. In the presence of manganese, an additional TGF-β-binding site is present in the TSP3 repeats of COMP. Finally, we show that COMP-bound TGF-β1 causes increased TGF-β1-dependent transcription. We conclude that TGF-β1 binds to COMP and that TGF-β1 bound to COMP has enhanced bioactivity.

原文英語
頁(從 - 到)43250-43258
頁數9
期刊Journal of Biological Chemistry
286
發行號50
DOIs
出版狀態已發佈 - 十二月 16 2011
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Haudenschild, D. R., Hong, E., Yik, J. H. N., Chromy, B., Mörgelin, M., Snow, K. D., Acharya, C., Takada, Y., & Di Cesare, P. E. (2011). Enhanced activity of transforming growth factor β1 (TGF-β1) bound to cartilage oligomeric matrix protein. Journal of Biological Chemistry, 286(50), 43250-43258. https://doi.org/10.1074/jbc.M111.234716