Ras signaling is important in many different cellular fate choices that occur during development, including alphabeta T cell maturation. Mice expressing a transgene encoding a dominant- negative form of Ras exhibit a reduction in the number of mature alphabeta T cells. As Ras has several effector pathways, these studies do not indicate which downstream cascades are involved in T cell maturation. One of these pathways, the ERK/MAPK cascade, has been shown to be necessary, but not sufficient for this process. It is the goal of this proposal to identify and characterize other signaling pathways required for Ras-mediated aplphabeta T cell maturation by analyzing the effects of various Ras effector mutants in an ex vivo model of T cell development.
