Signals via FGF receptor 2 regulate migration of endothelial cells.
Fibroblast growth factors (FGFs) stimulate angiogenesis, of which signals are transduced via FGF receptor (FGFR) tyrosine kinases. Although FGFR1 is a major receptor in endothelial cells, FGFR2 is frequently detectable in endothelial cells. We have previously demonstrated that the intracellular domain of FGFR1 sufficiently transduced signals leading to proliferation, migration, urokinase secretion, and tube formation. However, little is known about the roles of signaling via FGFR2 alone in endothelial cells. Murine brain capillary endothelial cells, denoted IBE cells, express small amounts of IIIc FGFR2, which is not activated by keratinocyte growth factor (KGF). We then transfected the IIIb FGFR2 in these cells. Three stable cell lines expressing IIIb FGFR2 demonstrated chemotaxis toward KGF, but never proliferated, secreted urokinase, or formed tube-like structure by KGF treatment. Weak but sustained activation of mitogen-activated protein kinase (MAPK) was observed in these cells. Chemotaxis toward KGF was significantly attenuated by treatment with PD98059. This is the first demonstration that signaling solely via FGFR2 in endothelial cells only contributes to motility through MAPK.
Nakamura
T
T
Department of Urology, Nagasaki University School of Medicine, Nagasaki, Japan.
Mochizuki
Y
Y
Kanetake
H
H
Kanda
S
S
D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D002633:Chemotaxis; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018919:Neovascularization, Physiologic; D011743:Pyrimidines / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
C412373:AG 1879; C496454:Fgf7 protein, mouse; D005419:Flavonoids; D011743:Pyrimidines; D017468:Receptors, Fibroblast Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one