Angiopoietin 2 stimulates migration and tube-like structure formation of murine brain capillary endothelial cells through c-Fes and c-Fyn.
The angiopoietin (Ang)/Tie2 system is exclusively involved in vasculogenesis and angiogenesis. Ang2 is known to inhibit Ang1-mediated phosphorylation of Tie2 as well as cellular responses during embryonic development. Recent studies have demonstrated that Ang2 has angiogenic activities in adult tissues and cultured endothelial cells. In the present study, we examined the downstream signaling pathways involved in Ang2-mediated cellular responses by murine brain capillary cell line, IBE cells. Tie2 was tyrosine phoshorylated by Ang2. Ang2 showed no effect on proliferation, but stimulated chemotaxis and tube-like structure formation. Phosphoinositide 3-kinase (PI 3-kinase) was activated by Ang2 through c-Fes and was involved in chemotaxis toward Ang2. Ang2 also activated c-Fyn in IBE cells. Cells expressing kinase-inactive c-Fyn attenuated Ang2-induced tube formation, suggesting that c-Fyn was responsible for Ang-2-mediated tube formation. Collecting these data, Ang2 activates c-Fes and c-Fyn, leading to migration and tube formation by murine capillary endothelial cells.
Mochizuki
Yasushi
Y
Department of Urology, Nagasaki University Graduate School of Medicine, 1-7-1, Sakamoto, Nagasaki 852-8501, Japan.
Nakamura
Takao
T
Kanetake
Hiroshi
H
Kanda
Shigeru
S
D042702:Angiopoietin-2; D000818:Animals; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000254:growth & development; D002455:Cell Division; D002460:Cell Line; D002633:Chemotaxis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D008163:Luminescent Measurements; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051578:Proto-Oncogene Proteins c-fes; D051076:Proto-Oncogene Proteins c-fyn; D042787:Receptor, TIE-2; D015398:Signal Transduction; D014162:Transfection
D042702:Angiopoietin-2; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C496646:Fes protein, mouse; C494960:Fyn protein, mouse; D051578:Proto-Oncogene Proteins c-fes; D051076:Proto-Oncogene Proteins c-fyn