GRB7: Proteins and Enzymes

Human Growth Factor Receptor-bound Protein 7 (GRB7) is a widely expressed, 532 amino acid (aa) member of the GRB7 family of adaptor proteins with a predicted molecular weight of 59.7 kDa. GRB7 contains an N-terminal proline-rich region, a central Pleckstrin homology domain, and a C-terminal Src-homology 2 (SH2) domain. The human protein shares 90% aa sequence identity with the mouse and rat orthologs. GRB7 localizes to the cytoplasm and the nucleus, but its nuclear localization is inhibited by Calmodulin. FAK phosphorylates GRB7 on Tyr188 and Tyr338 and these modifications are important for Integrin-dependent cell migration and proliferation. In contrast, hypophosphorylated GRB7 has been reported to play a role in the nuclear export of KOR mRNA. GRB7 also recruits and promotes the activation of the Ras signaling pathway in response to EGF. GRB7 enhances the phosphorylation of ErbB2 and Akt in breast cancer and is associated with high-grade ovarian cancer tumors, suggesting that it might play an important role in cancer. Furthermore, tyrosine-phosphorylated GRB7 interacts with HAX-1, which is a cytoskeletal-associated protein that can be overexpressed in metastatic tumors.