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Originally published In Press as doi:10.1074/jbc.M301028200 on March 3, 2003
J. Biol. Chem., Vol. 278, Issue 19, 16857-16862, May 9, 2003
37-kDa Laminin Receptor Precursor Modulates Cytotoxic Necrotizing
Factor 1-mediated RhoA Activation and Bacterial Uptake*
Jin Woong
Chung ,
Suk Jin
Hong§,
Kee Jun
Kim ,
Daniel
Goti ,
Monique F.
Stins ,
Sooan
Shin ,
Valina L.
Dawson§¶ **,
Ted M.
Dawson§¶**, and
Kwang Sik
Kim 
From the Departments of Pediatrics,
§ Neurology, ¶ Neuroscience, Physiology, and
** Institute for Cell Engineering, Johns Hopkins University,
School of Medicine, Baltimore, Maryland 21287
Cytotoxic necrotizing factor 1 (CNF1) is a
bacterial toxin known to activate Rho GTPases and induce host cell
cytoskeleton rearrangements. The constitutive activation of Rho GTPases
by CNF1 is shown to enhance bacterial uptake in epithelial cells and
human brain microvascular endothelial cells. However, it is unknown how exogenous CNF1 exhibits such phenotypes in eukaryotic cells. Here, we identified 37-kDa laminin receptor precursor (LRP) as
the receptor for CNF1 from screening the cDNA library of human brain microvascular endothelial cells by the yeast two-hybrid system
using the N-terminal domain of CNF1 as bait. CNF1-mediated RhoA
activation and bacterial uptake were inhibited by exogenous LRP or LRP
antisense oligodeoxynucleotides, whereas they were increased in
LRP-overexpressing cells. These findings indicate that the CNF1
interaction with LRP is the initial step required for CNF1-mediated
RhoA activation and bacterial uptake in eukaryotic cells.
*
This work was supported by grants from the National
Institutes of Health.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: Division of
Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Park 256, Baltimore, MD 21287. Tel.: 410-614-3917; Fax: 410-614-1491; E-mail: kwangkim@jhmi.edu.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

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