Extracellular Signal-regulated Kinase and the Small GTP-binding Protein, Rac, Contribute to the Effects of Transforming Growth Factor-β1 on Gene Expression

摘要: The kinases and regulatory proteins that convey signals initiated by transforming growth factor-beta (TGF-beta) to the nucleus are poorly characterized. To study role of extracellular signal-regulated kinase (ERK) pathway in this process, we transiently transfected NIH 3T3 fibroblasts with TGF-beta-responsive luciferase reporter genes expression vectors designed interrupt cascade. Mitogen-activated protein (MAP) phosphatase-1 a dominant negative MAP/ERK 1 mutant reduced stimulation plasminogen activator inhibitor-1 (PAI-1) promoter activity TGF-beta1 from 11.5- 4-fold 4.9-fold, respectively. Similar results were observed type I collagen promoters. increased ERK1 4.5-fold at 5 min 3. 1-fold 3 h, while Jun p38 not affected. Cotransfection small G protein, Rac, but Ras, Cdc42, or Rho mutants, effects on PAI-1 approximately half. In support for Rac signaling TGF-beta, GTP binding was 3.7-fold following exposure cells min. These findings indicate modulates gene partly through ERK cells.