Syndecans (SDCs) are transmembrane proteoglycans that are involved in cell adhesion and cell communication. Specifically, SDC2 plays a key role in tumorigenesis, metastasis, and angiogenesis. Previously, we found that rat SDC2 is shed by matrix metalloproteinase-7 (MMP-7) in colon cancer cells. Here, we analyzed the susceptibility of rat SDC2 to various MMPs. We found that the rat SDC2 ectodomain (ECD) fused to the C-terminal Fc region, which was expressed in mammalian cells, was cleaved more efficiently by MMP-14 than MMP-7. Likewise, when anchored on the surface of HeLa cells, rat SDC2 was cleaved more efficiently by the treatment of MMP-14 than MMP-7 and was shed more readily by membrane-anchored MMP-14 than soluble MMP-14. Furthermore, MMP-14 cleaved recombinant SDC2-ECD expressed in Escherichia coli into multiple fragments. Using N-terminal amino acid sequencing and the top-down proteomics approach, we determined that the major cleavage sites were S88↓L89, T98↓M99, T100↓L101, D132↓P133, and N148↓L149 for rat SDC2-ECD and S55↓G56, S65↓P66, P75↓K76, N92↓I93 D122↓P123, and S138↓L139 for human SDC2-ECD. Finally, the rat and human SDC2-ECD lost the ability to suppress vascular endothelial growth factor-induced formation of capillary-like tubes by human umbilical vein endothelial cells following cleavage by MMP-14, but its major cleavage-site mutant of rat SDC2-ECD did not. These results suggest that MMP-14 is a novel enzyme responsible for degrading SDC2 and impairing its physiological roles including angiogenesis.
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November 2017
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A 3D rendering of a mitochondrion. In this issue of the Biochemical Journal, Monteuuis et al. report that a conserved mammalian mitochondrial isoform of acetyl-CoA carboxylase ACC1 provides the malonyl-CoA essential for mitochondrial biogenesis in tandem with the mitochondrial malonyl-CoA synthetase ACSF3; see pages 3783–3797 for details.
Research Article|
November 01 2017
Processing of syndecan-2 by matrix metalloproteinase-14 and effect of its cleavage on VEGF-induced tube formation of HUVECs
Young Hun Lee;
Young Hun Lee
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
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Jun Hyoung Park;
Jun Hyoung Park
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
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Dong Huey Cheon;
Dong Huey Cheon
2Department of Biomedical Engineering, Sogang University, Seoul 04107, Republic of Korea
3Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
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Taeyoung Kim;
Taeyoung Kim
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
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Yae Eun Park;
Yae Eun Park
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
3Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
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Eok-Soo Oh;
Eok-Soo Oh
4Department of Life Sciences and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, Republic of Korea
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Ji Eun Lee;
Ji Eun Lee
3Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
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Seung-Taek Lee
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
Correspondence: Seung-Taek Lee (stlee@yonsei.ac.kr)
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Publisher: Portland Press Ltd
Received:
May 07 2017
Revision Received:
September 15 2017
Accepted:
September 25 2017
Accepted Manuscript online:
October 02 2017
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem J (2017) 474 (22): 3719–3732.
Article history
Received:
May 07 2017
Revision Received:
September 15 2017
Accepted:
September 25 2017
Accepted Manuscript online:
October 02 2017
Citation
Young Hun Lee, Jun Hyoung Park, Dong Huey Cheon, Taeyoung Kim, Yae Eun Park, Eok-Soo Oh, Ji Eun Lee, Seung-Taek Lee; Processing of syndecan-2 by matrix metalloproteinase-14 and effect of its cleavage on VEGF-induced tube formation of HUVECs. Biochem J 15 November 2017; 474 (22): 3719–3732. doi: https://doi.org/10.1042/BCJ20170340
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