Activation of RaIA is critical for Ras-induced tumorigenesis of human cells

RaIGEFs were recently shown to be critical for Ras-mediated transformed and tumorigenic growth of human cells. We now show that the oncogenic activity of these proteins is propagated by activation of one RaIGEF substrate, RaIA, but blunted by another closely related substrate, RaIB, and that the oncogenic signaling requires binding of the RaIBP1 and exocyst subunit effector proteins. Knockdown of RaIA expression impeded, if not abolished, the ability of human cancer cells to form tumors. RaIA was also commonly activated in a panel of cell lines from pancreatic cancers, a disease characterized by activation of Ras. Activation of RaIA signaling thus appears to be a critical step in Ras-induced transformation and tumorigenesis of human cells.