Igarashi K, Isohara T, Kato T, Shigeta K, Yamano T, Uno I
Life Science Research Center, Nippon Steel Corporation, Kawasaki, Japan.
Biochem Biophys Res Commun. 1998 May 8;246(1):95-9. doi: 10.1006/bbrc.1998.8578.
Vascular endothelial growth factor (VEGF) binds to its receptor tyrosine kinase Flt-1 and KDR/Flk-1 and stimulates their autophosphorylation. However, little is known about their downstream signal transduction properties. We examined the interactions of certain proteins with a SH2-domain with Flt-1 and KDR using the yeast two-hybrid system and found that Nck, SHP-2, PLC gamma, and PI3K p85 bind to Flt-1. Extensive site-directed mutagenesis of Flt-1 revealed their major binding sites. Nck, SHP-2, and PI3K bind to Y1213 of Flt-1. Nck also binds to Y1333 of Flt-1. These results suggest that Nck, SHP-2, PLC gamma, and PI3K play important roles in Flt-1 signal transduction and that Y1213 of Flt-1 is a major binding site of PI3K, Nck, and SHP-2.
血管内皮生长因子（VEGF）与其受体酪氨酸激酶Flt-1和KDR/Flk-1结合，并刺激它们的自身磷酸化。然而，对其下游信号转导特性了解甚少。我们使用酵母双杂交系统研究了某些含SH2结构域的蛋白质与Flt-1和KDR的相互作用，发现Nck、SHP-2、PLCγ和PI3K p85与Flt-1结合。对Flt-1进行广泛的定点诱变揭示了它们的主要结合位点。Nck、SHP-2和PI3K与Flt-1的Y1213结合。Nck还与Flt-1的Y1333结合。这些结果表明，Nck、SHP-2、PLCγ和PI3K在Flt-1信号转导中起重要作用，并且Flt-1的Y1213是PI3K、Nck和SHP-2的主要结合位点。
