PMID- 10373500
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 26
DP  - 1999 Jun 25
TI  - ADAMTS-1 is an active metalloproteinase associated with the extracellular matrix.
PG  - 18821-6
AB  - Cellular disintegrin and metalloproteinases (ADAMs) are a family of genes with a 
      sequence similar to the snake venom metalloproteinases and disintegrins. ADAMTS-1
      is a unique ADAM family protein with respect to the presence of thrombospondin
      type I motifs and the capacity to bind to the extracellular matrix. Because
      ADAMTS-1 has a potential zinc-binding motif in the metalloproteinase domain, we
      examined in this study whether ADAMTS-1 is an active metalloproteinase by means
      of the proteinase trapping mechanism of alpha2-macroglobulin. We found that the
      soluble type of ADAMTS-1 protein is able to form a covalent-binding complex with 
      alpha2-macroglobulin. Furthermore, the point mutation within the zinc-binding
      motif of ADAMTS-1 protein eliminates its capacity to bind to
      alpha2-macroglobulin. These data demonstrate that the metalloproteinase domain of
      ADAMTS-1 is catalytically active. In addition, we showed that the removal of the 
      pro-domain from the ADAMTS-1 precursor is impaired in the furin-deficient cell
      line, LoVo, and that the processing ability of the cells is restored by the
      co-expression of the furin cDNA. These data provide evidence that the ADAMTS-1
      precursor is processed in vivo by furin endopeptidase in the secretory pathway.
      Consequently, ADAMTS-1 is an active metalloprotease that is associated with the
      extracellular matrix. This study strongly suggests that ADAMTS-1 may play a role 
      in the inflammatory process through its protease activity.
FAU - Kuno, K
AU  - Kuno K
AD  - Department of Molecular Pharmacology, Cancer Research Institute, Kanazawa
      University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan.
      kkuno@kenroku.kanazawa-u.ac.jp
FAU - Terashima, Y
AU  - Terashima Y
FAU - Matsushima, K
AU  - Matsushima K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Disintegrins)
RN  - 0 (alpha-Macroglobulins)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (ADAMTS1 Protein)
RN  - EC 3.4.24.- (ADAMTS1 protein, human)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - ADAM Proteins
MH  - ADAMTS1 Protein
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Disintegrins/*metabolism
MH  - Extracellular Matrix/*enzymology
MH  - Glycosylation
MH  - Metalloendopeptidases/*metabolism
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - Protein Binding
MH  - Solubility
MH  - Zinc/metabolism
MH  - alpha-Macroglobulins/metabolism
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1074/jbc.274.26.18821 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 25;274(26):18821-6. doi: 10.1074/jbc.274.26.18821.