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Tyrosine 1213 of Flt-1 Is a Major Binding Site of Nck and SHP-2

1998; Elsevier BV; Volume: 246; Issue: 1 Linguagem: Inglês

10.1006/bbrc.1998.8578

1090-2104

Katsuhide Igarashi, Toshio Isohara, Toshiaki Kato, Keiko Shigeta, Tomoka Yamano, Isao Uno,

Protein Tyrosine Phosphatases

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.