The role of Gads in hematopoietic cell signalling.

Gads is a member of the family of SH2 and SH3 domain containing adaptor proteins that is expressed specifically in hematopoietic cells and functions in the coordination of tyrosine kinase mediated signal transduction. Gads plays a critical role in signalling from the T cell receptor by promoting the formation of a complex between SLP-76 and LAT. This complex couples the T cell receptor to Ras through a novel pathway involving PLC-gamma1, Tec family kinases, and RasGRP. Studies with Gads-deficient mice have highlighted its importance for thymocyte proliferation during T cell maturation. Emerging evidence suggests that Gads may also play additional roles in antigen-receptor signalling and receptor tyrosine kinase mediated signalling in other hematopoietic lineages. Gads is a unique member of the Grb2 adaptor family, because its activity can be regulated by caspase cleavage. Gads nucleates multi-protein complexes that are required for tyrosine kinase-dependent signalling in immune cells and may also represent a point of modulation for these pathways through the activation of caspase-dependent signalling events.