Neurofibromin, the product of the NF1 gene, is one of a family of GTPase-activating proteins (GAPs) that accelerate hydrolysis of active Ras-GTP to inactive Ras-GDP. Loss of neurofibromin (through mutations in NF1) causes a failure to terminate Ras signals and increases levels of active Ras. Our lab previously showed that Schwann cells cultured from human neurofibromas have high levels of active Ras. There are many (6) different members of the Ras protein family, that can affect different cellular responses, and a non-canonical Ras protein, TC21/R-Ras2 plays a role in tumor initiation, as described by Deanna Patmore, a previous graduate student in the laboratory. We are continuing elucidating the role of individual Ras proteins in Schwann cell tumor cells.