Logo array representing some of the known and unknown Gab-type proteins.

Domain Structure of GAB2
The Gab2 protein is a scaffolding protein attaching to inositol lipids at the cytoplasmic face of the plasma membrane through its PH domain, and serving as a scaffold, upon which an assortment of signaling proteins assemble. Gab2 contains 19 tyrosine amino acids along its length, which could serve as potential binding sites for SH2-domain containing proteins. Binding sites for 14-3-3 proteins also are present, as are up to five PxxP amino acid motifs with potential for interacting with SH3-domain containing proteins. The two C-terminal Tyrosines are known to interact with the SH2 domain(s) of the tyrosine phosphatase SHP-2. Three tyrosine sites that may interact with the p85 subunit of PI3kinase when phosphorylated are also highlighted.
The domain structure of the tyrosine phosphatase SHP-2, and a few of the Gab2-related proteins are shown at the left. SHP-2 contains two SH2 domains within its N-terminal segment and the PTB enzymatic domain removing phosphate from specific phosphotyrosine residues The Drosophila DOS protein was the first member of this group described. DOS is involved in growth factor receptor signaling from sevenless and is required for development of the ommatidial eye. The IRS-1 family of proteins were first described in Insulin signaling and may transmit developmental signals in that system. IRS-1 contains an additional domain, called PTB, for its propensity to bind additional phorphotyrosine motifs not recognized by SH2 domains. Finally, the Gab2 protein is shown. Gab2-related proteins include the better characterized Gab1, and at least two additional proteins yet uncharacterized, or unpublished.
How does Gab2 function in growth factor signaling?

The answer is not entirely clear, however, genetic evidence from Drosophila indicates that Gab2, like DOS, clearly controls the development of cells. Our hypothesis, based on the known and expected functions of the Gab-related protein family, is shown in the diagram to the right. The main features include: the positive coupling of the growth factor receptor, Fms, to Gab2 through the adaptor protein Grb2; The activation and signal transduction through Gab2, inducing specific gene expression; and finally, a not well understood "switch" between the Ras/MAPKinase pathway and the Gab2 mediated pathway. The details are currently being investigated and evaluated.