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Molecules 2014, 19(6), 8472-8487;

Matrilin-2 Is Proteolytically Cleaved by ADAMTS-4 and ADAMTS-5

Cell and Molecular Biology Laboratory, Department of Orthopaedics, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA
Department of Dermatology, Roger Williams Medical Center, Providence, RI 02908, USA
Authors to whom correspondence should be addressed.
Received: 8 April 2014 / Revised: 7 June 2014 / Accepted: 10 June 2014 / Published: 23 June 2014
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Matrilin-2 is a widely distributed, oligomeric extracellular matrix protein that forms a filamentous network by binding to a variety of different extracellular matrix proteins. We found matrilin-2 proteolytic products in transfected cell lines in vitro and in mouse tissues in vivo. Two putative cleavage sites were identified in the unique domain of matrilin-2; the first site was located between D851 and L852 in the middle of the domain and the second, at the boundary with the coiled-coil domain at the C-terminus. Deletion of the entire unique domain eliminated the proteolysis of matrilin-2. While the first cleavage site was present in all matrilin-2 oligomers, the second cleavage site became apparent only in the matrilin-2 hetero-oligomers with matrilin-1 or matrilin-3. Analysis using a variety of extracellular protease inhibitors suggested that this proteolytic activity was derived from a member or several members of the ADAMTS family. Recombinant human ADAMTS-4 (aggrecanase-1) and ADAMTS-5 (aggrecanase-2), but not ADAMTS-1, cleaved recombinant matrilin-2, thereby yielding matrilin-2 proteolytic peptides at the predicted sizes. These results suggest that ADAMTS-4 and ADAMTS-5 may destabilize the filamentous network in the extracellular matrix by cleaving matrilin-2 in both homo-oligomers and hetero-oligomers. View Full-Text
Keywords: matrilin-2; proteolytic cleavage; ADAMTS-4; ADAMTS-5; oligomerization matrilin-2; proteolytic cleavage; ADAMTS-4; ADAMTS-5; oligomerization

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Wang, Z.; Luo, J.; Iwamoto, S.; Chen, Q. Matrilin-2 Is Proteolytically Cleaved by ADAMTS-4 and ADAMTS-5. Molecules 2014, 19, 8472-8487.

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