Growth factor receptor-bound protein 2 (GRB2) is an ubiquitously-expressed, non-catalytic adaptor protein. Monomeric GRB2 is 25 kDa and consists of a central Src Homology 2 (SH2) (residues 60–152) domain flanked by two Src Homology 3 (SH3) domains (residues 1–58 and 156–215, respectively). The most well-studied role of GRB2 is its ability to bring disparate signaling molecules into close proximity and facilitate the formation of complexes important for signal transduction. The SH2 domain binds specific phosphorylated tyrosine residues on proteins, allowing GRB2 to associate broadly with molecules at the cell surface and plasma membrane, including growth factor receptors, cytokine receptors, CD28 co-stimulatory receptor, T cell receptor (TCR) ζ chains, and Linker for activation of T cells (LAT), among others. The terminal SH3 domains bind proline-rich regions on downstream signaling molecules such as SOS1, c-Cbl, Vav, and SLP-76, and more. Engagement of the TCR leads to phosphorylation of multiple tyrosine residues on the adaptor protein LAT, which in turn, serve as docking sites for various SH2 domain-bearing binding partners, including GRB2. Proper signal transmission depends critically on these early phosphorylation and rec
