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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-09

AUTHORS

Julia A. Romashkova, Sergei S. Makarov

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. More... »

PAGES

86

Journal

TITLE

Nature

ISSUE

6748

VOLUME

401

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/43474

DOI

http://dx.doi.org/10.1038/43474

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004390180

PUBMED

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


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