Akt is a downstream target of NF-kappa B.

Fanyin Meng, L. Liu, Paul C. Chin, Santosh R. D'Mello

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

The ubiquitously expressed transcription factor NF-kappa B 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-kappa B and Akt signaling pathways can converge. Indeed, I kappa B kinase, the kinase involved in NF-kappa B activation, is a substrate of Akt, and activation of Akt therefore stimulates NF-kappa B activity. Although these results place Akt upstream of NF-kappa B 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-kappa B. Treatment of NIH3T3 cells with the NF-kappa B activators, tumor necrosis factor (TNF) alpha and lipopolysaccharide, results in the stimulation of Akt phosphorylation. The stimulation of Akt is, however, detected only after I kappa B-alpha degradation is induced by these agents. The nuclear translocation of p65 and increased DNA binding activity of NF-kappa B also precede Akt phosphorylation. Treatment with two pharmacological inhibitors of NF-kappa B, SN50 and N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), blocks TNF-induced Akt activation. On the other hand TNF-mediated NF-kappa B 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-kappa B 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 I kappa B-alpha 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.

Original languageEnglish (US)
Pages (from-to)29674-29680
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number33
StatePublished - Aug 16 2002

Fingerprint

NF-kappa B
Phosphorylation
Chemical activation
I-kappa B Proteins
Tumor Necrosis Factor-alpha
Phosphotransferases
I-kappa B Kinase
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
1-Phosphatidylinositol 4-Kinase
Protein-Serine-Threonine Kinases
Phosphatidylinositols
Ketones
Phenylalanine
Lipopolysaccharides
Cell Survival
Transcription Factors
Cells
Pharmacology
Degradation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Meng, F., Liu, L., Chin, P. C., & D'Mello, S. R. (2002). Akt is a downstream target of NF-kappa B. Journal of Biological Chemistry, 277(33), 29674-29680.

Akt is a downstream target of NF-kappa B. / Meng, Fanyin; Liu, L.; Chin, Paul C.; D'Mello, Santosh R.

In: Journal of Biological Chemistry, Vol. 277, No. 33, 16.08.2002, p. 29674-29680.

Research output: Contribution to journalArticle

Meng, F, Liu, L, Chin, PC & D'Mello, SR 2002, 'Akt is a downstream target of NF-kappa B.', Journal of Biological Chemistry, vol. 277, no. 33, pp. 29674-29680.
Meng F, Liu L, Chin PC, D'Mello SR. Akt is a downstream target of NF-kappa B. Journal of Biological Chemistry. 2002 Aug 16;277(33):29674-29680.
Meng, Fanyin ; Liu, L. ; Chin, Paul C. ; D'Mello, Santosh R. / Akt is a downstream target of NF-kappa B. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 33. pp. 29674-29680.
@article{9666468d887d4c6385bf0d64b5ad5e16,
title = "Akt is a downstream target of NF-kappa B.",
abstract = "The ubiquitously expressed transcription factor NF-kappa B 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-kappa B and Akt signaling pathways can converge. Indeed, I kappa B kinase, the kinase involved in NF-kappa B activation, is a substrate of Akt, and activation of Akt therefore stimulates NF-kappa B activity. Although these results place Akt upstream of NF-kappa B 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-kappa B. Treatment of NIH3T3 cells with the NF-kappa B activators, tumor necrosis factor (TNF) alpha and lipopolysaccharide, results in the stimulation of Akt phosphorylation. The stimulation of Akt is, however, detected only after I kappa B-alpha degradation is induced by these agents. The nuclear translocation of p65 and increased DNA binding activity of NF-kappa B also precede Akt phosphorylation. Treatment with two pharmacological inhibitors of NF-kappa B, SN50 and N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), blocks TNF-induced Akt activation. On the other hand TNF-mediated NF-kappa B 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-kappa B 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 I kappa B-alpha 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.",
author = "Fanyin Meng and L. Liu and Chin, {Paul C.} and D'Mello, {Santosh R.}",
year = "2002",
month = "8",
day = "16",
language = "English (US)",
volume = "277",
pages = "29674--29680",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "33",

}

TY - JOUR

T1 - Akt is a downstream target of NF-kappa B.

AU - Meng, Fanyin

AU - Liu, L.

AU - Chin, Paul C.

AU - D'Mello, Santosh R.

PY - 2002/8/16

Y1 - 2002/8/16

N2 - The ubiquitously expressed transcription factor NF-kappa B 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-kappa B and Akt signaling pathways can converge. Indeed, I kappa B kinase, the kinase involved in NF-kappa B activation, is a substrate of Akt, and activation of Akt therefore stimulates NF-kappa B activity. Although these results place Akt upstream of NF-kappa B 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-kappa B. Treatment of NIH3T3 cells with the NF-kappa B activators, tumor necrosis factor (TNF) alpha and lipopolysaccharide, results in the stimulation of Akt phosphorylation. The stimulation of Akt is, however, detected only after I kappa B-alpha degradation is induced by these agents. The nuclear translocation of p65 and increased DNA binding activity of NF-kappa B also precede Akt phosphorylation. Treatment with two pharmacological inhibitors of NF-kappa B, SN50 and N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), blocks TNF-induced Akt activation. On the other hand TNF-mediated NF-kappa B 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-kappa B 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 I kappa B-alpha 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.

AB - The ubiquitously expressed transcription factor NF-kappa B 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-kappa B and Akt signaling pathways can converge. Indeed, I kappa B kinase, the kinase involved in NF-kappa B activation, is a substrate of Akt, and activation of Akt therefore stimulates NF-kappa B activity. Although these results place Akt upstream of NF-kappa B 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-kappa B. Treatment of NIH3T3 cells with the NF-kappa B activators, tumor necrosis factor (TNF) alpha and lipopolysaccharide, results in the stimulation of Akt phosphorylation. The stimulation of Akt is, however, detected only after I kappa B-alpha degradation is induced by these agents. The nuclear translocation of p65 and increased DNA binding activity of NF-kappa B also precede Akt phosphorylation. Treatment with two pharmacological inhibitors of NF-kappa B, SN50 and N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), blocks TNF-induced Akt activation. On the other hand TNF-mediated NF-kappa B 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-kappa B 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 I kappa B-alpha 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.

UR - http://www.scopus.com/inward/record.url?scp=0037119428&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037119428&partnerID=8YFLogxK

M3 - Article

VL - 277

SP - 29674

EP - 29680

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 33

ER -