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.