pubmed.ncbi.nlm.nih.gov

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

  • ️Fri Jan 01 1999

. 1999 Sep 2;401(6748):86-90.

doi: 10.1038/43474.

Affiliations

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

J A Romashkova et al. Nature. 1999.

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.

PubMed Disclaimer

Comment in

Similar articles

Cited by

Publication types

MeSH terms

Substances