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血管内皮管腔形成におけるc-Abl活性化：臼井一裕¹, 戸田憲一², 渋谷正史¹, 丸義朗¹(医科研・細胞遺伝¹, 京大・皮²）
　
c-Abl activation in endothelial tubulogenesis. :Kazuhiro USUI¹, Ken-ichi TODA², Masabumi SHIBUYA¹, Yoshiro MARU¹.(¹Dept.of Genetics, Inst.of Med.Sci., Univ.of Tokyo, ²Dept.of Derm., Univ.Kyoto)

Integrin-mediated signals induced by matrix ligands play a central role in angiogenesis, but precise mechanisms are still unknown. We have reported that activated VEGF receptor kinase(Flt-1) expression on non-tubulogenic cell line (NP31) caused tubulogenesis in basement membrane matrix (Matrigel) in concert with signals from matrix like Shc/MAP kinase activations. Here we show that Shc and cadherin-5 were phosphorylated by Matrigel stimulation to bind to Grb-2 in murine tubulogenic endothelial cell line F-2. We observed no difference in Matrigel-induced Shc phosphorylation between FAK(-/-) and wild type cells, suggesting the existence of FAK-independent pathways that lead to Shc phosphorylation. In F-2 cells, we found that c-Abl was not only activated as judged by in vitro kinase assay but also recruited with tyrosine-phosphorylated Shc in a Matrigel-dependent manner. The c-Abl was not autophosphorylated but was complexed to Shc. We introduced BCR/ABL into F-2 cells retrovirally to examine whether the continuous activation of c-Abl affects the integrin-mediated biology of endothelial cells or not. BCR/ABL expression in F-2 cells prolonged their survival and network formations on Matrigel. Given the fact that endothelial cells that participate in vascular structure are arrested at G1 stage of the cell cycle and that c-Abl negatively regulates cell growth, c-Abl may be one of the signal mediators of endothelial differentiation.