ABSTRACT
148The GRB2 family of proteins consists of three highly related homologs, GRB2, GADS, and GRAP. These proteins have a conserved domain structure with a central SH2 domain, which binds to phosphorylated tyrosine ligands, flanked by two SH3 domains, which interact with proline- or arginine/lysine-rich sequences in numerous signaling proteins. The function of the GRB2 family of proteins is to regulate signaling events by connecting phosphorylated ligands, such as receptor tyrosine kinases and adaptor proteins, to downstream effectors needed for the propagation of intracellular signaling. Because of these functions, the GRB2 family of proteins is critical for the differentiation and function of numerous cell types, as well as for the initiation and progression of a panoply of human diseases. GRB2, GADS, and GRAP are especially vital for the function of T cells. These proteins control signaling complexes at the T cell antigen receptor and the adaptor protein LAT, where they facilitate the activation, differentiation, and function of T cells. This chapter will describe the domain structure of the GRB2 family of proteins, their general role in the initiation of signaling in multiple cell types, and their function in the activation and differentiation of T cells.
