A recent report suggested that platelet-derived growth factor (PDGF) activates nuclear factor-κB (NF-κB) by phosphorylation of the protein kinase Akt [Romashkova and Makarov, Nature 401 (1999) 86–90]. The present study investigates the role of Akt in the activation of NF-κB by tumor necrosis factor-α (TNFα, 10 ng/ml) and PDGF-BB (20 ng/ml) in human vascular smooth muscle cells (SMC), skin and foreskin fibroblasts. TNFα stimulated serine phosphorylation and degradation of the inhibitory protein IκBα and strongly induced nuclear NF-κB translocation and binding activity. PDGF did not induce serine phosphorylation or degradation of IκBα and did not enhance binding activity of NF-κB. In contrast, stimulation with PDGF resulted in a marked phosphorylation of Akt, but no Akt phosphorylation occurred after stimulation with TNFα. These data suggest that Akt phosphorylation is not involved in NF-κB activation in human SMC and fibroblasts.
