GRB-associated binder (Gab) is a family of adaptor proteins recruited by a wide variety of receptor tyrosine kinases (RTKs), such as EGFR, HGFR, insulin receptor, cytokine receptor and B cell antigen receptors. Upon stimulation of RTKs by their cognate ligand, Gab is recruited to the plasma membrane, undergoes phosphorylation and functions as a multiprotein assembling center (1-4). Multiple tyrosine phosphorylation sites of Gab1 protein have been identified (5). Phosphorylation of tyrosine 472 regulates its binding to p85 PI3 kinase (6,7). Phosphorylation of tyrosines 307, 373 and 407 modulates the association to PLCgamma (8). Phosphorylation of tyrosines 627 and 659 are required for the binding and activation of protein tyrosine phosphatase SHP2 (6,9). Gab2 is also phosphorylated by tyrosine kinases (10,11). Tyrosine 452 is a potential binding site of p85, the regulatory subunit of PI3 kinase. Tyrosine 614 is essential for SHP2 association (11). Furthermore, Akt phosphorylates Gab2 at serine 149 and inhibits Gab2 tyrosine phosphorylation, suggesting that Akt is engaged in negative feedback regulation of Gab2 signaling (12).