Many growth factors function by binding receptors with intrinsic tyrosine kinase activity. Signaling by such receptors involves a series of intermediates characterized by SH2 domains that bind tyrosine phosphorylated receptors by a direct interaction between the SH2 domain and the phosphotyrosine-containing receptor sequences. GRB7, a SH2 domain protein, has a single SH2 domain at its C-terminal, a central region with similarity to Ras GAP and a proline-rich N-terminus. GRB7 maps to the region on mouse chromosome 11 containing the Neu gene. This region of mouse chromosome 11 is syntenic to an area of human chromosome 17q that is frequently amplified in breast cancer. Moreover, GRB7 is amplified and over-expressed in breast cancer and is found in a complex with Neu gp185.
