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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 LaiDagger , Shu-Chen KaoDagger , Si-Tse Jiang§, Ming-Jer Tang§, Po-Chao ChanDagger , and Hong-Chen ChenDagger

From the Dagger  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 alpha 2 and, to a lesser extent, alpha 3 in Madin-Dardy canine kidney cells and that a monoclonal antibody against integrin alpha 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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