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Molecules 2014, 19(6), 8472-8487; doi:10.3390/molecules19068472

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

1
Cell and Molecular Biology Laboratory, Department of Orthopaedics, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA
2
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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Abstract

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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MDPI and ACS Style

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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