The role of Gads in hematopoietic cell signalling

Gads is a member of the family of SH2 and SH3 domain containing adaptor pro teins that is expressed specifically in hematopoietic cells and functions i n the coordination of tyrosine kinase mediated signal transduction. Gads pl ays 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 fami ly kinases, and RasGRP. Studies with Gads-deficient mice have highlighted i ts importance for thymocyte proliferation during T cell maturation. Emergin g evidence suggests that Gads may also play additional roles in antigen-rec eptor 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 multiprotein complexes that are required for tyrosine kinase-dependent sign alling in immune cells and may also represent a point of modulation for the se pathways through the activation of caspase-dependent signalling events.