Recruitment of Gab proteins to activated receptors and the main effector arms of Gab signalling. The indirect mode of recruitment applies to all receptors except c-Met (see text and Fig. 3 for details). Characteristics of this mechanism are that phosphotyrosine residues within the cytoplasmic tails of activated surface receptors serve as docking sites for the SH2 domain of Grb2, which in turn binds via its C-terminal SH3 domain to specific binding sites in Gab1-3. Alternatively, Shc can serve as additional bridging molecules between Gab and activated receptors. Membrane/receptor association leads to tyrosine phosphorylation of Gab proteins and subsequent recruitment of SH2 domain-containing effectors such as SHP2, p85, PLCγ and Crk. While it has been shown by numerous studies that the association between Gab proteins and the effectors Shp2, p85, Grb2, Crk and PLCγ represents a direct protein-protein interaction, the coupling between Gab and STAT5 needs to be resolved in the future.