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, Hong Chen Chen

研究成果: Article同行評審

71 引文 斯高帕斯(Scopus)


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 α2 and, to a lesser extent, α3 in Madin-Dardy canine kidney cells and that a monoclonal antibody against integrin α2 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 p130(Cas) 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.

頁(從 - 到)7474-7480
期刊Journal of Biological Chemistry
出版狀態Published - 2000 3月 17

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子生物學
  • 細胞生物學


深入研究「Involvement of focal adhesion kinase in hepatocyte growth factor-induced scatter of Madin-Darby canine kidney cells」主題。共同形成了獨特的指紋。