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

Nature | Sep 2, 1999

http://www.ncbi.nlm.nih.gov/pubmed/10485711

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. Platelet-derived growth factor (PDGF) is a principal survival factor that inhibits apoptosis and promotes proliferation, but the mechanisms mediating its anti-apoptotic properties are not completely understood. Here we show that the transcription factor NF-kappaB is important in PDGF signalling. NF-kappaB 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-kappaB through Ras and phospatidylinositol-3-kinase (PI(3)K) to the PKB/Akt protein kinase and the IkappaB kinase (IKK); NF-kappaB thus appears to be a target of the anti-apoptotic Ras/PI(3)K/Akt pathway. We show that, upon PDGF stimulation, Akt transiently associates in vivo with IKK and induces IKK activation. These findings establish a role for NF-kappaB in growth factor signalling and define an anti-apoptotic Ras/PI(3)K/Akt/IKK/NF-kappaB pathway, thus linking anti-apoptotic signalling with transcription machinery.

Pubmed ID: 10485711 RIS Download

Mesh terms: 3T3 Cells | Animals | Apoptosis | Catalysis | Cell Division | Cells, Cultured | DNA | Gene Expression Regulation | Humans | I-kappa B Kinase | Mice | Mitogens | Mutation | NF-kappa B | Phosphatidylinositol 3-Kinases | Platelet-Derived Growth Factor | Protein Binding | Protein-Serine-Threonine Kinases | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-akt | Proto-Oncogene Proteins c-myc | Rats | Recombinant Proteins | Signal Transduction | Transfection | ras Proteins

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