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J Biol Chem, Vol. 275, Issue 11, 7474-7480, March 17, 2000
Involvement of Focal Adhesion Kinase in Hepatocyte Growth
Factor-induced Scatter of Madin-Darby Canine Kidney Cells*
Jui-Fen
Lai ,
Shu-Chen
Kao ,
Si-Tse
Jiang§,
Ming-Jer
Tang§,
Po-Chao
Chan , and
Hong-Chen
Chen ¶
From the Department of Zoology, National Chung Hsing
University, Taichung 40227, Taiwan and the § Department of
Physiology, National Cheng Kung University Medical College, Tainan
70101, Taiwan, Republic of China
Focal adhesion kinase (FAK) has been implicated
to play a critical role in integrin-mediated control of cell behavior.
However, it is unclear whether FAK also participates in the regulation of growth factor-elicited cellular functions. In this study, we have
demonstrated that although overexpression of FAK in Madin-Dardy canine
kidney cells did not alter their growth property or ability to form
tubules within collagen gel upon hepatocyte growth factor (HGF)
stimulation, it apparently enhanced HGF-induced cell scattering. This
enhancement was largely because of an increase in the third phase
(i.e. cell migration) of cell scattering rather than the first two phases (i.e. cell spreading and cell-cell
dissociation). Conversely, the expression of FAK-related nonkinase
significantly (~60%) inhibited HGF-induced cell migration. Moreover,
we have found that the effect of FAK on promoting HGF-induced cell
motility was greatly dependent on cell-matrix interactions. We showed
that HGF treatment selectively increased the expression of integrins 2 and, to a lesser extent, 3 in
Madin-Dardy canine kidney cells and that a monoclonal antibody against
integrin 2 efficiently blocked HGF-enhanced cell
migration on collagen. In our efforts to determine the mechanism by
which FAK promotes HGF-induced cell migration, we found that FAK
mutants deficient in phosphatidylinositol 3-kinase or
p130Cas binding failed to promote HGF-induced cell
migration. Interestingly, cells expressing a FAK mutant defective in
Grb2 binding exhibited a rate of migration ~50% lower than that of
cells expressing wild type FAK in response to HGF stimulation. Taken
together, our results suggest a link between HGF-increased integrin
expression, FAK activation, and enhanced cell motility and implicate a
role for FAK in the facilitation of growth factor-induced cell motility.
*
This work was supported by National Science Council, Taiwan,
Grant NSC89-2311-B005-031 (to H.-C. C.).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. Tel.:
886-4-2854922; Fax: 886-4-2851797; E-mail: hcchen@nchu.edu.tw.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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