Involvement of focal adhesion kinase in hepatocyte growth factor-induced scatter of Madin-Darby canine kidney cells.
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 ( approximately 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 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 approximately 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.
Lai
J F
JF
Department of Zoology, National Chung Hsing University, Taichung 40227, Taiwan.
Kao
S C
SC
Jiang
S T
ST
Tang
M J
MJ
Chan
P C
PC
Chen
H C
HC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein; D004285:Dogs; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051380:GRB2 Adaptor Protein; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D016023:Integrins / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D038981:Receptors, Collagen; D011994:Recombinant Proteins / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D050719:Crk-Associated Substrate Protein; D016326:Extracellular Matrix Proteins; D005419:Flavonoids; D051380:GRB2 Adaptor Protein; D016023:Integrins; D010750:Phosphoproteins; D011506:Proteins; D038981:Receptors, Collagen; D011994:Recombinant Proteins; D050717:Retinoblastoma-Like Protein p130; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one