 It is thus not surprising that targeted gene disruption of Grb2 in mice is lethal at an early embryonic stage.Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2.Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain.