THE GRB2 ADAPTER

Grb2 is an 'adaptor' protein made of one SH2 and two SH3 domains, The SH3 domains bind to prolinerich motifs in the C-terminal part of the r as exchange factor Sos. Binding of the Grb2 SH2 domain to phosphotyros ine motifs on receptors, or other adaptor proteins such as Shc, recrui ts this Grb2/Sos complex at the plasma membrane where Sos stimulates n ucleotide exchange on ras, then ras activates raf and leads to MAP kin ase activation. The structure of Grb2, the precise motifs recognised b y its SH2 and SH3 domains, the way Grb2 performs its function, a possi ble regulation of its association with Sos, and its ability to complex with other proteins in vivo, are discussed.