Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2

Biochem Biophys Res Commun. 1998 May 8;246(1):95-9. doi: 10.1006/bbrc.1998.8578.

Abstract

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.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • DNA Primers / genetics
  • Intracellular Signaling Peptides and Proteins
  • Isoenzymes / metabolism
  • Mutagenesis, Site-Directed
  • Oncogene Proteins / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phospholipase C gamma
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / metabolism*
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / chemistry*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Saccharomyces cerevisiae / genetics
  • Signal Transduction
  • Transformation, Genetic
  • Type C Phospholipases / metabolism
  • Tyrosine / chemistry
  • Vascular Endothelial Growth Factor Receptor-1
  • src Homology Domains

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA Primers
  • Intracellular Signaling Peptides and Proteins
  • Isoenzymes
  • Nck protein
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Tyrosine
  • Receptor Protein-Tyrosine Kinases
  • Vascular Endothelial Growth Factor Receptor-1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Type C Phospholipases
  • Phospholipase C gamma