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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 B [3-5] 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 Ras 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.

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