Fibroblast growth factor-2 induces the activation of Src through Fes, which regulates focal adhesion disassembly.
Cell migration is regulated by focal adhesion (FA) turnover. Fibroblast growth factor-2 (FGF-2) induces FA disassembly in the murine brain capillary endothelial cell line IBE, leading to FGF-2-directed chemotaxis. We previously showed that activation of Src and Fes by FGF-2 was involved in chemotaxis of IBE cells. In this study, we examined the interplay between Src and Fes. FGF-2 treatment decreased the number of FA in IBE cells, but not in cells expressing dominant-negative Fes (denoted KE5-15 cells). FGF-2 induced the activation of Src and subsequent binding to and phosphorylation of Cas in IBE cells, but not in KE5-15 cells. Focal adhesion kinase (FAK) activation and tyrosine phosphorylation by Src were also delayed in KE5-15 cells compared to parental cells. FGF-2 induced activation of Src within FA in IBE cells, but not in KE5-15 cells. Downregulation of Fes or FAK using small interfering RNA diminished Src activation by FGF-2 within FA. These findings suggest that activation of Fes by FGF-2 enhances FAK-dependent activation of Src within FA, promoting FGF-2-induced disassembly of focal adhesions.
Kanda
Shigeru
S
Department of Molecular Microbiology and Immunology, Division of Endothelial Cell Biology, Nagasaki University Graduate School of Biomedical Science, Japan. skanda-jua@umin.net
Miyata
Yasuyoshi
Y
Kanetake
Hiroshi
H
Smithgall
Thomas E
TE
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects* / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D019000:Phosphotyrosine / Q000378:metabolism; D051578:Proto-Oncogene Proteins c-fes / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects
D034741:RNA, Small Interfering; D016222:Fibroblast Growth Factor 2; D019000:Phosphotyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051578:Proto-Oncogene Proteins c-fes; D016392:Proto-Oncogene Proteins pp60(c-src)