Akt Is a Downstream Target of NF-κB*
By F. Meng, Li Liu, P. C. Chin, S. D’Mello. Journal of Biological Chemistry, 2002
172 citations recorded by the source corpus.
The ubiquitously expressed transcription factor NF-κB and the serine-threonine kinase Akt both are involved in the promotion of cell survival. Although initially believed to operate as components of distinct signaling pathways, several studies have demonstrated that the NF-κB and Akt signaling pathways can converge. Indeed, IκB kinase, the kinase involved in NF-κB activation, is a substrate of Akt, and activation of Akt therefore stimulates NF-κB activity. Although these results place Akt upstream of NF-κB activation in the sequence of signaling events, we report that this may not necessarily be the case and that Akt is a downstream target of NF-κB. Treatment of NIH3T3 cells with the NF-κB activators, tumor necrosis factor (TNF) α and lipopolysaccharide, results in the stimulation of Akt phosphorylation. The stimulation of Akt is, however, detected only after IκB-α degradation is induced by these agents. The nuclear translocation of p65 and increased DNA binding activity of NF-κB also precede Akt phosphorylation. Treatment with two pharmacological inhibitors of NF-κB, SN50 andN-tosyl-l-phenylalanine chloromethyl ketone (TPCK), blocks TNF-induced Akt activation. On the other hand TNF-mediated NF-κB activation is not reduced by the phosphoinositide-3 kinase inhibitors wortmannin and LY294002, although these inhibitors completely block the activation of Akt. These results suggest that NF-κB is required for TNF-mediated Akt activation and that it lies upstream of the stimulation of Akt. Consistent with this conclusion is the finding that overexpression of p65/RelA leads to Akt phosphorylation in the absence of extracellular stimulatory factors, whereas overexpression of IκB-α reduces Akt phosphorylation below basal levels. Interestingly, in addition to stimulating the phosphorylation of Akt, overexpression of p65 causes an increase in the expression of Akt mRNA and protein.
Subfields: Cancer Research, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/99b01f3019a516823675ec61418f607c3d81affb
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
Citations in the corpus
- NF-κB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: potential involvement of ZEB-1 and ZEB-2 (2007, background): “Consistent with the previous report (Meng et al., 2002), AKT-1 was induced by p65 (Figure 1c, right panel).”