Expression of Rac1b stimulates NF-κB-mediated cell survival and G1/S progression

The small GTPase Rac1 can stimulate various signaling pathways following a tightly controlled GDP-GTP exchange. A splicing variant designated Rac1b was found to exist predominantly in the active GTP-bound state but the functional consequences of its expression remain unknown. Here we used mouse fibroblasts as a model to assess the signaling properties of Rac1b. We show that, in contrast to Rac1, expression of wild-type Rac1b is sufficient to stimulate cyclin D1 accumulation and G1/S progression in these cells. Moreover, expression of wild-type Rac1b, but not of wild-type Rac1, dramatically increased cell survival in the presence of only minimal growth stimuli. Both cellular responses were blocked by the NF-κB super-repressor IκBα(A32A36). Active Rac1b induced the phosphorylation and membrane translocation of IκBα, a prerequisite for the activation of NF-κB. These data demonstrate that Rac1b is a highly active Rac1 variant that stimulates cell cycle progression and cell survival in pathways involving NF-κB.