| Background |
GRB2-associated-binding protein 2 (Gab2) belongs to the Gab family of signaling scaffolds, which are characterized by a highly conserved N-terminal PH domain for membrane recruitment, multiple proline-rich motifs for the recruitment of SH3 domain-containing proteins, such as GRB2, and multiple tyrosine residues capable of associating with SH2 domain-containing proteins, such as p85 PI3K, CrkL, and SHP-2, in a phosphorylation-dependent manner Research studies have shown that Gab2 is a widely expressed protein that participates in orchestrating signals downstream of many transmembrane receptors for growth factors and cytokines Indeed, Gab2 was initially identified as a tyrosine-phosphorylated protein associated with SHP-2 and the p85 subunit of PI3K in response to engagement of the IL-3 and M-CSF receptors Subsequent studies also identified Gab2 as a participant in signaling cascades triggered by the T cell antigen receptor It is now well established that Gab2 is a critical component of signaling cascades triggered by numerous oncogenic tyrosine kinases. In the context of human disease, Gab2 has been shown to be overexpressed in breast cancer and ovarian cancer, which facilitates tumor cell proliferation and survival.
|