Endostatin-induced tyrosine kinase signaling through the Shb adaptor protein regulates endothelial cell apoptosis.
作者： Johan Dixelius , Helena Larsson , Takako Sasaki , Kristina Holmqvist , Lingge Lu
DOI: 10.1182/BLOOD.V95.11.3403
关键词:
摘要: Endostatin, which corresponds to the C-terminal fragment of collagen XVIII, is a potent inhibitor angiogenesis. Fibroblast growth factor-2 (FGF-2)-induced angiogenesis in chicken chorioallantoic membrane was inhibited by endostatin, but not an endostatin mutant R158/270A, lacking heparin-binding ability. Endostatin internalized endothelial cells, mouse fibroblasts. Treatment murine brain (IBE) cells with reduced proportion S phase, whereas growth-arrested IBE gels treated displayed enhanced tubular morphogenesis. overexpressing Shb, adaptor protein implicated angiostatin-induced apoptosis, elevated apoptosis and decreased morphogenesis response when added together FGF-2. Induction dependent on ability expression Shb functional Src homology 2 (SH2)-domain. treatment for 10 minutes or 24 hours induced tyrosine phosphorylation formation multiprotein complexes. An SH2 domain fusion precipitated 125-kd phosphotyrosyl endostatin-treated cells. The component either contained intrinsic kinase activity occurred complex kinase. In conclusion, our data show that induces FGF-treated
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