The nonreceptor protein-tyrosine kinase c-Fes is involved in fibroblast growth factor-2-induced chemotaxis of murine brain capillary endothelial cells. Export

@article{citeulike:2188750, abstract = {Fibroblast growth factor-2 (FGF-2)-induced migration of endothelial cells is involved in angiogenesis in vivo. However, signal transduction pathways leading to FGF-2-induced chemotaxis of endothelial cells are largely unknown. Previous studies have shown that the cytoplasmic protein-tyrosine kinase c-Fes is expressed in vascular endothelial cells and may influence angiogenesis in vivo. To investigate the contribution of c-Fes to FGF-2 signaling, we expressed wild-type or kinase-inactive human c-Fes in the murine brain capillary endothelial cell line, IBE (Immortomouse brain endothelial cells). Wild-type c-Fes was tyrosine-phosphorylated upon FGF-2-stimulation in transfected cells, whereas kinase-inactive c-Fes was not. Overexpression of wild-type c-Fes promoted FGF-2-independent tube formation of IBE cells. Tube formation was not observed with endothelial cells expressing kinase-inactive c-Fes, indicating a requirement for c-Fes kinase activity in this biological response. Expression of kinase-defective c-Fes suppressed endothelial cell migration following FGF-2 treatment, suggesting that activation of endogenous c-Fes may be required for the chemotactic response. Expression of either wild-type c-Fes or the kinase-inactive mutant did not affect the tyrosine phosphorylation FRS2, Shc, or phospholipase C-gamma, nor did it influence the kinetics of mitogen-activated protein kinase activation. These results implicate c-Fes in FGF-2-induced chemotaxis of endothelial cells through signaling pathways not linked to mitogenesis.}, address = {Department of Urology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. shigeruk@net.nagasaki-u.ac.jp}, author = {Kanda, S. and Lerner, E. C. and Tsuda, S. and Shono, T. and Kanetake, H. and Smithgall, T. E.}, citeulike-article-id = {2188750}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/10744691}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=10744691}, day = {7}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {arap-3, immorto\_mice}, month = {April}, number = {14}, pages = {10105--10111}, posted-at = {2008-01-02 16:54:48}, priority = {2}, title = {The nonreceptor protein-tyrosine kinase c-Fes is involved in fibroblast growth factor-2-induced chemotaxis of murine brain capillary endothelial cells.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/10744691}, volume = {275}, year = {2000} }

TY - JOUR ID - citeulike:2188750 L3 - citeulike-article-id:2188750 N2 - Fibroblast growth factor-2 (FGF-2)-induced migration of endothelial cells is involved in angiogenesis in vivo. However, signal transduction pathways leading to FGF-2-induced chemotaxis of endothelial cells are largely unknown. Previous studies have shown that the cytoplasmic protein-tyrosine kinase c-Fes is expressed in vascular endothelial cells and may influence angiogenesis in vivo. To investigate the contribution of c-Fes to FGF-2 signaling, we expressed wild-type or kinase-inactive human c-Fes in the murine brain capillary endothelial cell line, IBE (Immortomouse brain endothelial cells). Wild-type c-Fes was tyrosine-phosphorylated upon FGF-2-stimulation in transfected cells, whereas kinase-inactive c-Fes was not. Overexpression of wild-type c-Fes promoted FGF-2-independent tube formation of IBE cells. Tube formation was not observed with endothelial cells expressing kinase-inactive c-Fes, indicating a requirement for c-Fes kinase activity in this biological response. Expression of kinase-defective c-Fes suppressed endothelial cell migration following FGF-2 treatment, suggesting that activation of endogenous c-Fes may be required for the chemotactic response. Expression of either wild-type c-Fes or the kinase-inactive mutant did not affect the tyrosine phosphorylation FRS2, Shc, or phospholipase C-gamma, nor did it influence the kinetics of mitogen-activated protein kinase activation. These results implicate c-Fes in FGF-2-induced chemotaxis of endothelial cells through signaling pathways not linked to mitogenesis. IS - 14 JF - J Biol Chem SN - 0021-9258 AD - Department of Urology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. shigeruk@net.nagasaki-u.ac.jp EP - 10111 TI - The nonreceptor protein-tyrosine kinase c-Fes is involved in fibroblast growth factor-2-induced chemotaxis of murine brain capillary endothelial cells. VL - 275 SP - 10105 KW - arap-3 KW - immorto_mice AU - Kanda, S AU - Lerner, EC AU - Tsuda, S AU - Shono, T AU - Kanetake, H AU - Smithgall, TE PY - 2000/04/07/ UR - http://view.ncbi.nlm.nih.gov/pubmed/10744691 ER -