GAB2: Proteins and Enzymes

Human GRB2-associated Binding Protein 2 (GAB2) is a 676 amino acid (aa) member of the GAB family of adapter proteins with a predicted molecular weight of 74.5 kDa and an apparent weight of 95 kDa via SDS-PAGE. The human proteins shares 92% and 91% aa sequence identity with the mouse and rat orthologs, respectively. GAB2 contains an N-terminal Pleckstrin homology domain and a central proline-rich domain. It is ubiquitously expressed with the highest levels found in brain, kidney, lung, heart, testis, and ovary. GAB2 mediates many cellular processes such as proliferation, survival, migration, and differentiation. Accordingly, it is important for the activation of multiple signaling pathways including the PI 3-Kinase/Akt and MAPK pathways. Multiple tyrosine residues within GAB2 can be phosphorylated, leading to activation of downstream signaling following interaction with many plasma membrane receptors including receptor tyrosine kinases, cytokine receptors, Fc receptors, T and B cell receptors, and G protein-coupled receptors. GAB2 can also be negatively regulated via phosphorylation. Akt-dependent phosphorylation of Ser159, ERK-dependent phosphorylation of Ser623, and growth factor-dependent phosphorylation of Ser210 and Thr391 have all been reported to suppress GAB2-dependent signaling. GAB2 likely plays an important role in cancer. It has been reported to regulate tumor angiogenesis in N-Ras-driven melanoma, amplify Bcr-Abl signaling in chronic myeloid leukemia, and promote metastasis in breast cancer.