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J. Biol. Chem., Vol. 277, Issue 40, 37637-37646, October 4, 2002
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From the Departamento de Bioquímica y
Biología Molecular, Instituto Universitario de
Oncología, Universidad de Oviedo, 33006 Oviedo, Spain
We have identified and cloned a fetal liver
cDNA encoding a new serine proteinase that has been called
matriptase-2. This protein exhibits a domain organization similar to
other members of an emerging family of membrane-bound serine
proteinases known as type II transmembrane serine proteinases.
Matriptase-2 contains a short cytoplasmic domain, a type II
transmembrane sequence, a central region with several modular
structural domains including two CUB (complement
factor C1s/C1r, urchin embryonic growth factor, bone morphogenetic protein) domains and three low density
lipoprotein receptor tandem repeats, and finally, a C-terminal
catalytic domain with all typical features of serine proteinases. The
human matriptase-2 gene maps to 22q12-q13, a location that differs from
all type II transmembrane serine proteinase genes mapped to date.
Immunofluorescence and Western blot analysis of COS-7 cells transfected
with the isolated cDNA confirmed that matriptase-2 is anchored to
the cell surface. Matriptase-2 was expressed in Escherichia
coli, and the purified recombinant protein hydrolyzed synthetic
substrates used for assaying serine proteinases and endogenous proteins
such as type I collagen, fibronectin, and fibrinogen.
Matriptase-2 could also activate single-chain urokinase plasminogen
activator, albeit with low efficiency. These activities were abolished
by inhibitors of serine proteinases but not by inhibitors of other
classes of proteolytic enzymes. Northern blot analysis demonstrated
that matriptase-2 transcripts are only detected at significant levels in both fetal and adult liver, suggesting that this novel serine proteinase may play a specialized role in matrix remodeling processes taking place in this tissue during development or in adult tissues.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AJ319876.
Matriptase-2, a Membrane-bound Mosaic Serine Proteinase
Predominantly Expressed in Human Liver and Showing Degrading Activity
against Extracellular Matrix Proteins*
,§,
*
This work was supported by Grant SAF00-0217 from
Comisión Interministerial de Ciencia y Tecnología-Spain
and European Union (QLG1-CT-2000-01131). The Instituto Universitario de
Oncología was supported by Obra Social Cajastur-Asturias.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.
These authors contributed equally to this manuscript.
§
Recipients of research contracts from Ministerio de Ciencia y
Tecnología, Spain.
¶
To whom correspondence should be addressed: Departamento de
Bioquímica y Biología Molecular, Facultad de Medicina,
Universidad de Oviedo, 33006 Oviedo, Spain. Tel.: 34-985-104201;
Fax: 34-985-103564; E-mail: CLO@correo.uniovi.es.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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