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

The mechanisms of cell proliferation and transformation are intrinsically linked to the process of apoptosis: the default of proliferating cells is to die unless specific survival signals are provided(1,2). Platelet-derived growth factor (PDGF) is a principal survival factor that inhibits apoptosis and promotes proliferation(1), but the mechanisms mediating its anti-apoptotic properties are not completely understood. Here we show that the transcription factor NF-kappa B3-5 is important in PDGF signalling. NF-kappa B transmits two signals: one is required for the induction of proto-oncogene c-myc and proliferation, and the second, an anti-apoptotic signal, counterbalances c-Myc cytotoxicity. We have traced a putative pathway whereby PDGF activates 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). We show that, upon PDGF stimulation, Akt transiently associates in vivo with IKK and induces IKK activation. These findings establish a role for NF-kappa B in growth factor signalling and define an anti-apoptotic Ras/PI(3)K/Akt/IKK/NF-kappa B pathway, thus linking anti-apoptotic signalling with transcription machinery.