title: Downregulation of Fes inhibits VEGF-A-induced chemotaxis and capillary-like morphogenesis by cultured endothelial cells.
abstract: The aim of this study was to determine whether the downregulation of endogenous Fes by siRNA in cultured endothelial cells affects vascular endothelial growth factor-A (VEGF-A)-induced chemotaxis and capillary-like morphogenesis, which are considered as angiogenic cellular responses in vitro. VEGF-A-treatment induced autophosphorylation of Fes in cultured endothelial cells. LY294002, a phosphoinositide 3-kinase inhibitor, significantly inhibited VEGF-A-induced chemotaxis and capillary-like morphogenesis. Downregulation of Fes attenuated these VEGF-A-induced cellular responses but LY294002 did not produce further inhibition of these responses. Downregulation of Fes neither affected VEGF-A-induced autophosphorylation of VEGF receptor 2 nor mitogen-activated protein kinase activation, but markedly decreased Akt activation. Taken together, our novel results indicate the involvement of Fes in VEGF-A-induced cellular responses by cultured endothelial cells.
authors.affiliation: Department of Molecular Microbiology and Immunology, Division of Endothelial Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. skanda-jua@umin.net
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kanda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanetake
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Miyata
mesh_terms: D002196:Capillaries / Q000187:drug effects / Q000196:embryology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051578:Proto-Oncogene Proteins c-fes / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C496645:FES protein, human; D051578:Proto-Oncogene Proteins c-fes; D051057:Proto-Oncogene Proteins c-akt