Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor

Biochem J. 1999 Jul 1;341 ( Pt 1)(Pt 1):211-6.


In this paper we demonstrate the presence of two novel in vivo autophosphorylation sites in the c-Kit/stem cell factor receptor (c-Kit/SCFR): Tyr-703 in the kinase insert and Tyr-936 in the C-terminal tail. We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936. It is shown that the association occurs through the Src homology 2 (SH2) domains of Grb2 and Grb7. Binding of Grb2 to Tyr-703 in the c-Kit/SCFR provides a link to the Ras/mitogen-activated protein kinase pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • GRB2 Adaptor Protein
  • GRB7 Adaptor Protein
  • Humans
  • Phosphorylation
  • Protein Binding
  • Proteins / metabolism*
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Stem Cell Factor
  • Tyrosine*
  • src Homology Domains


  • Adaptor Proteins, Signal Transducing
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • GRB7 protein, human
  • Proteins
  • Recombinant Fusion Proteins
  • Stem Cell Factor
  • GRB7 Adaptor Protein
  • Tyrosine
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases