Tyrosine 1213 of Flt-1 Is a Major Binding Site of Nck and SHP-2☆
1998
Abstract Vascular endothelial growth factor (VEGF) binds to its receptor tyrosine kinases 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, PLCγ, 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, PLCγ, 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.
Keywords:
- PI3K/AKT/mTOR pathway
- Autophosphorylation
- Receptor tyrosine kinase
- Cancer research
- Vascular endothelial growth factor
- Signal transduction
- Binding site
- Molecular biology
- Biology
- Two-hybrid screening
- SH2 domain
- Biochemistry
- Tyrosine
- Receptor Protein-Tyrosine Kinases
- Protein tyrosine phosphatase
- Phosphatidylinositol 3-Kinases
- Correction
- Source
- Cite
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