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J. Biol. Chem., Vol. 276, Issue 27, 24549-24556, July 6, 2001
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From the Department of Medical Specialties, The University of Texas
Health Center, Tyler, Texas 75708
Interaction between the urokinase-type
plasminogen activator (uPA) and its receptor (uPAR) localizes cellular
proteolysis and promotes cellular proliferation and migration. The
interaction between uPA and uPAR at the surface of epithelial cells
thereby contributes to the pathogenesis of lung inflammation and
neoplasia. In this study, we sought to determine if uPA itself alters
uPAR expression by lung epithelial cells. uPA enhanced uPAR expression as well as 125I-uPA binding in Beas2B lung epithelial
cells in a time- and concentration-dependent manner. The
uPA-mediated induction of uPAR is not accomplished through its receptor
and requires enzymatic activity. The low molecular weight fragment of
uPA, lacking the receptor binding domain, was as potent as intact
two-chain uPA in inducing expression of uPAR at the cell surface.
Plasmin, the end product of plasminogen activation, did not alter
uPA-mediated uPAR expression. Induction of uPAR by uPA represents a
novel pathway by which epithelial cells can regulate
uPAR-dependent cellular responses that may contribute to
stromal remodeling in lung injury or neoplasia.
Urokinase Induces Expression of Its Own Receptor in Beas2B Lung
Epithelial Cells*
and
*
This work was supported by NHLBI Grant R01-HL-62453-01 from
the National Institutes of Health (to S. S.), and Grant R01
45018-06 (to S. I.).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.
To whom correspondence should be addressed: Dept. of Medical
Specialties, The University of Texas Health Center at Tyler, Lab C-6,
Biomedical Research Bldg., 11937 U.S. Highway 271, Tyler, TX 75708. Tel.: 903-877-7668; Fax: 903-877-5627; E-mail:
sreerama.shetty@uthct.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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