Molecular Cloning of a Gene Encoding a New Type of Metalloproteinase-disintegrin Family Protein with Thrombospondin Motifs as an Inflammation Associated Gene*
- From the Department of Pharmacology, ‡ Cancer Research Institute,
- § Hospital Pharmacy, Kanazawa University, Kanazawa, Japan
- ¶ To whom correspondence should be addressed: Dept. of Pharmacology, Cancer Research Institute, Kanazawa University, Takara-Machi 13-1, Kanazawa, Ishikawa 920, Japan. Tel.: 81-762-62-8151 (ext. 5454); Fax: 81-762-60-7704; E-mail: koujim{at}kenroku.ipc.kanazawa-u.ac.jp
Abstract
A cellular disintegrin and metalloproteinase (ADAM) is a new family of genes with structural homology to the snake venom metalloproteinases
and disintegrins. We screened genes which were selectively expressed in the cachexigenic colon 26 adenocarcinoma subline in vivo. It was found that one novel cDNA clone, identified as a cachexigenic tumor selective gene, encodes a cysteine-rich protein
which shows a sequence similarity to that of both the snake venom metalloproteinases and thrombospondins. We named this cDNA
clone 
isintegrin 
nd 
etalloproteinase with 
hrombo
pondin motifs (ADAMTS-1). ADAMTS1 consists of six domains, 1) a pro- and 2) a metalloproteinase, 3) a disintegrin-like, 4)
a thrombospondin (TSP) homologous domain containing TSP type I motif, 5) a spacer region, and 6) COOH-terminal TSP submotifs.
Unlike other ADAMs, ADAMTS-1 does not possess a transmembrane domain and is a putative secretory protein. Therefore, ADAMTS-1
is a new type of ADAM family protein with TSP type I motifs. We demonstrated that the TSP homologous domain containing the
TSP type I motif of ADAMTS-1 is functional for binding to heparin. ADAMTS-1 mRNA could be induced by stimulating colon 26
cells with an inflammatory cytokine, interleukin-1, in vitro. Moreover, intravenous administration of lipopolysaccharide in mice selectively induced ADAMTS-1 mRNA in kidney and heart.
These data suggest that ADAM-TS-1 may be a gene whose expression is associated with various inflammatory processes as well
as development of cancer cachexia.
Footnotes
-
↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- ADAM
-
a disintegrin and metalloproteinase
- IL
-
interleukin
- LPS
-
lipopolysaccharide
- PCR
-
polymerase chain reaction
- TSP
-
thrombospondin
- kb
-
kilobase pair(s)
- GST
-
glutathione S-transferase.
-
↵2K. Kuno, N. Kanada, E. Nakashima, F. Fujiki, F. Ichimura, and K. Matsushima, unpublished results.
-
- Received July 3, 1996.
- © 1997 by The American Society for Biochemistry and Molecular Biology, Inc.
