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

Romashkova, Julia A., Makarov, Sergei S.·1999·Nature
DOI 10.1038/43474
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Abstract

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.

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Research works printed but not linked: 30

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Metadata

Authors
Romashkova, J. A., & Makarov, S. S.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
1999-09
Volume
401
Issue
6748
Pages
86-90
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/43474
Cited by
1,517
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

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