Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor.
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.
Thömmes
K
K
Ludwig Institute for Cancer Research, Biomedicum, Box 595, S-751 24 Uppsala, Sweden.
Lennartsson
J
J
Carlberg
M
M
Rönnstrand
L
L
D048868:Adaptor Proteins, Signal Transducing; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D051380:GRB2 Adaptor Protein; D051382:GRB7 Adaptor Protein; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019089:Stem Cell Factor; D014443:Tyrosine; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495955:GRB7 protein, human; D011506:Proteins; D011993:Recombinant Fusion Proteins; D019089:Stem Cell Factor; D051382:GRB7 Adaptor Protein; D014443:Tyrosine; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases