Identification of Tyr-703 and Tyr-936 as the primary association sites forGrb2 and Grb7 in the c-Kit/stem cell factor receptor

In this paper we demonstrate the presence of two novel in vivo autophosphor ylation 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 dem onstrate that the adapter protein Grb2 is a specific binding partner for bo th phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter p rotein Grb7 binds selectively to phosphorylated Tyr-936. It is shown that t he 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 R as/mitogen-activated protein kinase pathway.