GRB2 is an adapter protein that contains a central SH2 domain flanked by N- and C-terminal SH3 domains. GRB2 acts downstream of receptor protein-tyrosine kinases and is involved in Ras and MAP kinase pathway activation by associating with the guanine exchange factor (GEF) SOS. GRB2 is constitutively bound to SOS through its SH3 domains, which interact with a proline-rich sequence in the C-terminal part of SOS (Chardin et al. 1993). Following phosphorylation of LAT, the GRB2:SOS complex binds to the phosphorylated tyrosines and is thereby translocated to the inner face of the plasma membrane where inactive RAS:GDP resides. The three distal tyrosines, Y171, Y191 and Y226 of LAT are responsible for GRB2 association (Balagopalan et al. 2010, Zhang et al. 2000).