Grb2

Grb2 is an adaptor protein involved in signal transduction/cell communication. The name Grb2 is an abbreviation of Growth factor receptor-bound protein 2.

Function and expression
Grb2 is widely expressed and is essential for multiple cellular functions. Inhibition of Grb2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types, and so it is not surprising that a targeted gene disruption of Grb2 in mouse is lethal at an early embryonic stage. Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction.

Domains
The SH2 domain of Grb2 binds to phosphorylated tyrosine containing peptides on receptors or scaffold proteins with a preference for pY-X-N-X, where X is generally a hydrophobic residue such as valine (see The SH2 Website).

The N-terminal SH3 domain binds to proline-rich peptide peptides and can bind to the Ras-guanine exchange factor SOS.

The C-terminal SH3 domain binds to peptides conforming to a P-X-I/L/V/-D/N-R-X-X-K-P motif that allows it to specifically bind to proteins such as Gab-1.