NF-kappa B is a target of AKT in anti-apoptotic PDGF signalling

The mechanisms of cell proliferation and transformation are intrinsically l inked to the process of apoptosis: the default of proliferating cells is to die unless specific survival signals are provided(1,2). Platelet-derived g rowth factor (PDGF) is a principal survival factor that inhibits apoptosis and promotes proliferation(1), but the mechanisms mediating its anti-apopto tic properties are not completely understood. Here we show that the transcr iption factor NF-kappa B3-5 is important in PDGF signalling. NF-kappa B tra nsmits two signals: one is required for the induction of proto-oncogene c-m yc and proliferation, and the second, an anti-apoptotic signal, counterbala nces c-Myc cytotoxicity. We have traced a putative pathway whereby PDGF act ivates NF-kappa B through pas and phospatidylinositol-3-kinase (PI(3)K) to the PKB/Akt protein kinase and the I kappa B kinase (IKK); NF-kappa B thus appears to be a target of the anti-apoptotic Ras/PI(3)K/Akt pathway(6,7). W e show that, upon PDGF stimulation, Akt transiently associates in vivo with IKK and induces IKK activation. These findings establish a role for NF-kap pa B in growth factor signalling and define an anti-apoptotic Ras/PI(3)K/Ak t/IKK/NF-kappa B pathway, thus linking anti-apoptotic signalling with trans cription machinery.