Vascular Endothelial Cell Growth Factor Promotes Tyrosine Phosphorylation of Mediators of Signal Transduction That Contain SH2 Domains

摘要: Vascular endothelial cell growth factor (VEGF), an cell-specific mitogen that plays important role in angiogenesis, promotes the tyrosine phosphorylation of at least 11 proteins bovine aortic cells (BAEC). Proteins immunoprecipitated from lysates control- and VEGF-stimulated BAEC with antisera to phospholipase C- γ (PLC- γ) were fractionated by SDS-polyacrylamide gel electrophoresis transferred Immobilon-P. Evaluation Western blots phosphotyrosine demonstrated PLC- γ two (100 85 kDa) associate phosphorylated response VEGF. By using specific other mediators signal transduction contain SH2 domains for immunoprecipitation, it was VEGF phosphatidylinositol 3-kinase, Ras GTPase activating protein (GAP), oncogenic adaptor NcK. Mr consistent receptors Flt-1 Flk-1/KDR also stimulated cells. Tyrosine-phosphorylated Nck, PLC- γ, GAP-associated proteins, p190 p62, GAP immunoprecipitates BAEC, tyrosine-phosphorylated NcK 3-kinase immunoprecipitates. These observations suggest formation multimeric aggregates activate various signaling pathways. VEGF-promoted proliferation domain containing molecules inhibited kinase inhibitor genistein.