Angiotensin II activates Akt/protein kinase B by an arachidonic acid/redox‐dependent pathway and independent of phosphoinositide 3‐kinase

Lupeol exhibits multiple pharmacological activities including, anticancerous, anti-inflammatory, and antioxidant. The aim of this study was to explore the anticancerous activity of lupeol on ovarian cancer cells and examine its mechanism of action. To this end, increasing concentrations of lupeol on cell viability, cell cycle, and apoptosis in Caov-3 cells were evaluated. Lupeol inhibited cell viability, induced G1 phase arrest in cell cycle, increased cell apoptosis, and inhibited the ratio of phospho-Akt/protein kinase B and phospho-mammalian target of rapamycin/mammalian target of rapamycin. In conclusion, these data suggest that lupeol may play a therapeutic role in ovarian cancer.

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Lovastatin inhibits the growth and survival pathway of phosphoinositide 3-kinase/protein kinase B in immortalized rat brain neuroblasts

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2005.03345.x ◽

2005 ◽

Vol 94 (5) ◽

pp. 1277-1287 ◽

Cited By ~ 16

Author(s):

Maria Isabel Cerezo-Guisado ◽

Luis Jesus Garcia-Marin ◽

Maria Jesus Lorenzo ◽

Maria Julia Bragado

Keyword(s):

Protein Kinase ◽

Rat Brain ◽

Protein Kinase B ◽

Growth And Survival ◽

Survival Pathway ◽

Phosphoinositide 3 Kinase

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Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase B

Digestive Diseases and Sciences ◽

10.1007/s10620-013-2666-1 ◽

2013 ◽

Vol 58 (8) ◽

pp. 2197-2204 ◽

Cited By ~ 13

Author(s):

Guoqing Pan ◽

Zhu Zhu ◽

Jian Huang ◽

Chenggang Yang ◽

Ying Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Protein Kinase ◽

Plasminogen Activator ◽

Protein Kinase B ◽

Cancer Invasion ◽

Type Plasminogen Activator ◽

Urokinase Type Plasminogen Activator ◽

Phosphoinositide 3 Kinase ◽

Semaphorin 5A

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Osthole protects against inflammation in a rat model of chronic kidney failure via suppression of nuclear factor-κB, transforming growth factor-β1 and activation of phosphoinositide 3-kinase/protein kinase B/nuclear factor (erythroid-derived 2)-like 2 signaling

Molecular Medicine Reports ◽

10.3892/mmr.2017.7125 ◽

2017 ◽

Vol 16 (4) ◽

pp. 4915-4921 ◽

Cited By ~ 6

Author(s):

Tao Huang ◽

Zhen Dong

Keyword(s):

Growth Factor ◽

Protein Kinase ◽

Rat Model ◽

Transforming Growth Factor ◽

Protein Kinase B ◽

Chronic Kidney Failure ◽

Nuclear Factor Κb ◽

Transforming Growth Factor Β1 ◽

Nuclear Factor ◽

Phosphoinositide 3 Kinase

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Activation of the Phosphatidylinositol 3-Kinase-Akt/Protein Kinase B Signaling Pathway in Arachidonic Acid-stimulated Human Myeloid and Endothelial Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m103250200 ◽

2001 ◽

Vol 276 (29) ◽

pp. 27246-27255 ◽

Cited By ~ 28

Author(s):

Charles S. T. Hii ◽

Nahid Moghadammi ◽

Andrew Dunbar ◽

Antonio Ferrante

Keyword(s):

Endothelial Cells ◽

Arachidonic Acid ◽

Protein Kinase ◽

Signaling Pathway ◽

Protein Kinase B ◽

Phosphatidylinositol 3 Kinase ◽

Phosphatidylinositol 3

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Upregulation of phosphoinositide 3-kinase and protein kinase B in alveolar macrophages following ozone inhalation. Role of NF-кB and STAT-1 in ozone-induced nitric oxide production and toxicity

Oxygen/Nitrogen Radicals: Cell Injury and Disease ◽

10.1007/978-1-4615-1087-1_10 ◽

2002 ◽

pp. 91-98 ◽

Cited By ~ 1

Author(s):

Debra L. Laskin ◽

Ladan Fakhrzadeh ◽

Diane E. Heck ◽

Donald Gerecke ◽

Jeffrey D. Laskin

Keyword(s):

Nitric Oxide ◽

Protein Kinase ◽

Alveolar Macrophages ◽

Protein Kinase B ◽

Nitric Oxide Production ◽

Oxide Production ◽

Phosphoinositide 3 Kinase

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Domain Swapping Used To Investigate the Mechanism of Protein Kinase B Regulation by 3-Phosphoinositide-Dependent Protein Kinase 1 and Ser473 Kinase

Molecular and Cellular Biology ◽

10.1128/mcb.19.7.5061 ◽

1999 ◽

Vol 19 (7) ◽

pp. 5061-5072 ◽

Cited By ~ 75

Author(s):

Mirjana Andjelković ◽

Sauveur-Michel Maira ◽

Peter Cron ◽

Peter J. Parker ◽

Brian A. Hemmings

Keyword(s):

Protein Kinase ◽

Kinase Inhibitors ◽

Protein Kinase B ◽

Second Messengers ◽

Activation Mechanism ◽

Dependent Protein Kinase ◽

Dependent Protein ◽

Phosphoinositide 3 Kinase ◽

Regulatory Sites

ABSTRACT Protein kinase B (PKB or Akt), a downstream effector of phosphoinositide 3-kinase (PI 3-kinase), has been implicated in insulin signaling and cell survival. PKB is regulated by phosphorylation on Thr308 by 3-phosphoinositide-dependent protein kinase 1 (PDK1) and on Ser473 by an unidentified kinase. We have used chimeric molecules of PKB to define different steps in the activation mechanism. A chimera which allows inducible membrane translocation by lipid second messengers that activate in vivo protein kinase C and not PKB was created. Following membrane attachment, the PKB fusion protein was rapidly activated and phosphorylated at the two key regulatory sites, Ser473 and Thr308, in the absence of further cell stimulation. This finding indicated that both PDK1 and the Ser473 kinase may be localized at the membrane of unstimulated cells, which was confirmed for PDK1 by immunofluorescence studies. Significantly, PI 3-kinase inhibitors prevent the phosphorylation of both regulatory sites of the membrane-targeted PKB chimera. Furthermore, we show that PKB activated at the membrane was rapidly dephosphorylated following inhibition of PI 3-kinase, with Ser473 being a better substrate for protein phosphatase. Overall, the results demonstrate that PKB is stringently regulated by signaling pathways that control both phosphorylation/activation and dephosphorylation/inactivation of this pivotal protein kinase.

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