The Shc proteins have been implicated in the Ras signaling pathway by virtue of their association with the Grb2 adaptor molecule. Several lines of evidence indicate that this association is indeed involved in Ras activation. More recent experiments in mammalian tissue culture cells suggest that domains unique to Shc isoforms, named CH1 and CH2, might be involved in a new network of protein-protein interactions, and hint at other roles that Shc might play in addition to Ras activation.