Expression of Rac1b stimulates NF-kappaB-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-kappaB super-repressor IkappaBalpha(A32A36). Active Rac1b induced the phosphorylation and membrane translocation of IkappaBalpha, a prerequisite for the activation of NF-kappaB. These data demonstrate that Rac1b is a highly active Rac1 variant that stimulates cell cycle progression and cell survival in pathways involving NF-kappaB.
Matos
Paulo
P
Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal.
Jordan
Peter
P
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002470:Cell Survival; D016193:G1 Phase; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport / Q000502:physiology; D016196:S Phase; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020830:rac1 GTP-Binding Protein
D020672:I-kappa B Proteins; D016328:NF-kappa B; D009479:Neuropeptides; C107953:RAC1 protein, human; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein