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{alpha}1-antitrypsin Inhibits the Activity of the Matriptase Catalytic Domain in vitro.

Janciauskiene, Sabina LU ; Nita, Izabela LU ; Subramaniyam, Devipriya LU ; Li, Qian; Lancaster Jr, Jack R and Matalon, Sadis (2008) In American Journal of Respiratory Cell and Molecular Biology 39(6). p.631-637
Abstract
Matriptase is a type II transmembrane protease which is characterized by an N-terminal transmembrane and multiple extracellular domains, in addition to the conserved extracellular serine protease catalytic domain. The expression pattern of matriptase suggests that this protease may play broad roles in the biology of surface lining epithelial cells. In this study we report that alpha1-antitrypsin (AAT), an endogenous inhibitor of serine proteases, inhibits the catalytic domain of human recombinant matriptase in vitro. Co-incubation of alpha1-antitrypsin with matriptase (at a molar ratio 1:2) resulted in the formation of heat stable complexes, clearly seen in sodium dodecyl sulfate (SDS) electrophoresis and Western blots. AAT was found to be... (More)
Matriptase is a type II transmembrane protease which is characterized by an N-terminal transmembrane and multiple extracellular domains, in addition to the conserved extracellular serine protease catalytic domain. The expression pattern of matriptase suggests that this protease may play broad roles in the biology of surface lining epithelial cells. In this study we report that alpha1-antitrypsin (AAT), an endogenous inhibitor of serine proteases, inhibits the catalytic domain of human recombinant matriptase in vitro. Co-incubation of alpha1-antitrypsin with matriptase (at a molar ratio 1:2) resulted in the formation of heat stable complexes, clearly seen in sodium dodecyl sulfate (SDS) electrophoresis and Western blots. AAT was found to be a slow, tight-binding inhibitor of the catalytic domain of matriptase with a second order reaction rate constant of 0.31 x10(3) M(-1)s(-1). Notably, the oxidised form of AAT, which lacks serine protease inhibitor activity, failed to generate matriptase complexes and to inhibit matriptase activity. Since matriptase is involved in a number of physiological processes including activation of epithelial sodium channels, our findings offer considerable new insights into new regulatory function of AAT in vivo. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
matriptase, alpha(1)-antitrypsin, serine proteases, complex formation, kinetics
in
American Journal of Respiratory Cell and Molecular Biology
volume
39
issue
6
pages
631 - 637
publisher
American Thoracic Society
external identifiers
  • wos:000261259500001
  • pmid:18723439
  • scopus:57349149443
ISSN
1535-4989
DOI
10.1165/rcmb.2008-0015RC
language
English
LU publication?
yes
id
19ad1175-12e4-44f5-ae90-0e1fdac0eb8f (old id 1222966)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18723439?dopt=Abstract
date added to LUP
2008-09-03 12:18:02
date last changed
2017-11-12 03:20:35
@article{19ad1175-12e4-44f5-ae90-0e1fdac0eb8f,
  abstract     = {Matriptase is a type II transmembrane protease which is characterized by an N-terminal transmembrane and multiple extracellular domains, in addition to the conserved extracellular serine protease catalytic domain. The expression pattern of matriptase suggests that this protease may play broad roles in the biology of surface lining epithelial cells. In this study we report that alpha1-antitrypsin (AAT), an endogenous inhibitor of serine proteases, inhibits the catalytic domain of human recombinant matriptase in vitro. Co-incubation of alpha1-antitrypsin with matriptase (at a molar ratio 1:2) resulted in the formation of heat stable complexes, clearly seen in sodium dodecyl sulfate (SDS) electrophoresis and Western blots. AAT was found to be a slow, tight-binding inhibitor of the catalytic domain of matriptase with a second order reaction rate constant of 0.31 x10(3) M(-1)s(-1). Notably, the oxidised form of AAT, which lacks serine protease inhibitor activity, failed to generate matriptase complexes and to inhibit matriptase activity. Since matriptase is involved in a number of physiological processes including activation of epithelial sodium channels, our findings offer considerable new insights into new regulatory function of AAT in vivo.},
  author       = {Janciauskiene, Sabina and Nita, Izabela and Subramaniyam, Devipriya and Li, Qian and Lancaster Jr, Jack R and Matalon, Sadis},
  issn         = {1535-4989},
  keyword      = {matriptase,alpha(1)-antitrypsin,serine proteases,complex formation,kinetics},
  language     = {eng},
  number       = {6},
  pages        = {631--637},
  publisher    = {American Thoracic Society},
  series       = {American Journal of Respiratory Cell and Molecular Biology},
  title        = {{alpha}1-antitrypsin Inhibits the Activity of the Matriptase Catalytic Domain in vitro.},
  url          = {http://dx.doi.org/10.1165/rcmb.2008-0015RC},
  volume       = {39},
  year         = {2008},
}