title: Role of c-Fyn in FGF-2-mediated tube-like structure formation by murine brain capillary endothelial cells.
abstract: Tube formation of endothelial cells is an important step of angiogenesis. However, little is known about the molecular mechanisms underlying growth factor-mediated tube formation by endothelial cells. FGF-2 stimulates tube formation by a murine brain capillary endothelial cell line, IBE cells, when cultured on collagen gels (differentiation-associated culture condition), whereas cells proliferate and migrate without forming tube on fibronectin-coated surface (proliferation/migration-associated condition). To elucidate FGF-2-mediated signal transduction pathways leading to tube formation by endothelial cells, we focused on the contribution of Src family kinases. Src family kinase inhibitor PP2 attenuated FGF-2-induced tube formation. Stable expression of kinase-inactive c-Src in IBE cells demonstrated no dominant negative effect on FGF-2-induced tube formation. In vitro kinase assay revealed that c-Fyn was activated by FGF-2 only in cells cultured on collagen gels. Three independent cell lines, expressing kinase-inactive c-Fyn, all exhibited attenuation of FGF-2-mediated tube formation. However, FGF-2-mediated proliferation or migration was not clearly perturbed in these cells. These results show the first time that c-Fyn plays a pivotal role in tube formation by endothelial cells.
authors.affiliation: Department of Urology, Nagasaki University School of Medicine, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsuda
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtsuru
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanetake
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kanda
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000254:growth & development; D002460:Cell Line; D004730:Endothelium, Vascular / Q000254:growth & development*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: C412373:AG 1879; D004791:Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases