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MTOR PRKAB2 (1 - 3 of 3)
PMID: 21470048
Stimulation of cardiomyogenesis of embryonic stem cells by nitric oxide downstream of AMP-activated protein kinase and mTOR signaling pathways.
... when AMPK was either activated by ... or mTOR was ...   (details)

MTOR PRKAB2

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  AMPK   (PRKAA1   PRKAA2   PRKAB1   PRKAB2   PRKAG1   PRKAG2 )

PMID: 21470048

Stimulation of cardiomyogenesis of embryonic stem cells by nitric oxide downstream of AMP-activated protein kinase and mTOR signaling pathways.
Source

Stem cells and development (December 2011)

Abstract

Stimulation of cardiomyogenesis of embryonic stem cells by nitric oxide downstream of AMP-activated protein kinase and mTOR signaling pathways. Nitric oxide (NO) is a key regulator of cardiomyogenesis of embryonic stem (ES) cells. However, signaling pathways involving the energy sensor AMP-activated protein kinase (AMPK) and/or mammalian target of rapamycin (mTOR) resulting in NO generation and stimulation of cardiomyogenesis are currently not known. Herein, the role of AMPK- versus mTOR-regulated signaling pathways and the impact of NO for cardiomyogenesis of mouse ES cells were investigated. Activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAr) or metformin as well as inactivation of AMPK by compound C (Comp C), siRNA ablation of AMPKa2, or exogenous ATP stimulated cardiomyogenesis of ES cells. Inhibition of AMPK by Comp C resulted in phosphorylation of mTOR and generation of NO. NO generation was likewise achieved when AMPK was either activated by AICAr or mTOR was inhibited by rapamycin, suggesting that NO generation occurred by two mutually active parallel signaling pathways, one being AMPK dependent and mTOR independent (AICAr pathway) and the other being AMPK independent and mTOR dependent (Comp C pathway). Consequently, cardiomyogenesis as well as NO generation was completely abrogated when ES cells were cultivated in the presence of rapamycin and Comp C, which inhibit both signaling pathways. The impact of NO for cardiomyogenesis of ES cells was corroborated in experiments showing that the effects of Comp C on cardiomyogenesis of ES cells were abolished by the NO synthase inhibitors NG-monomethyl-l-arginine and N (G) -nitro-l-arginine methyl ester. In summary, our data demonstrate that NO generation downstream of AMPK and mTOR is activated by distinct, interacting signaling pathways that initiate cardiomyogenesis of ES cells.

PMID: 22875991
Translation suppression promotes stress granule formation and cell survival in response to cold shock.
... concomitant activation of AMP-activated protein kinase (AMPK), ... of mTOR signaling.   (details)

MTOR PRKAB2

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Cause:  mTOR-signaling   (RPTOR   MTOR )
Theme:  AMPK   (PRKAA1   PRKAA2   PRKAB1   PRKAB2   PRKAG1   PRKAG2 )

PMID: 22875991

Translation suppression promotes stress granule formation and cell survival in response to cold shock.
Source

Molecular biology of the cell (October 2012)

Abstract

Translation suppression promotes stress granule formation and cell survival in response to cold shock. Cells respond to different types of stress by inhibition of protein synthesis and subsequent assembly of stress granules (SGs), cytoplasmic aggregates that contain stalled translation preinitiation complexes. Global translation is regulated through the translation initiation factor eukaryotic initiation factor 2a (eIF2a) and the mTOR pathway. Here we identify cold shock as a novel trigger of SG assembly in yeast and mammals. Whereas cold shock-induced SGs take hours to form, they dissolve within minutes when cells are returned to optimal growth temperatures. Cold shock causes eIF2a phosphorylation through the kinase PERK in mammalian cells, yet this pathway is not alone responsible for translation arrest and SG formation. In addition, cold shock leads to reduced mitochondrial function, energy depletion, concomitant activation of AMP-activated protein kinase (AMPK), and inhibition of mTOR signaling. Compound C, a pharmacological inhibitor of AMPK, prevents the formation of SGs and strongly reduces cellular survival in a translation-dependent manner. Our results demonstrate that cells actively suppress protein synthesis by parallel pathways, which induce SG formation and ensure cellular survival during hypothermia.

PMID: 23061908
Grape polyphenols inhibit akt/mammalian target of rapamycin signaling and potentiate the effects of gefitinib in breast cancer.
... induce the ... of AMPK, ... inhibit mTOR signaling in ...   (details)

MTOR PRKAB2

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Cause:  mTOR-signaling   (MLST8   RPTOR   MTOR )
Theme:  AMPK   (PRKAA1   PRKAA2   PRKAB1   PRKAB2   PRKAG1   PRKAG2 )

PMID: 23061908

Grape polyphenols inhibit akt/mammalian target of rapamycin signaling and potentiate the effects of gefitinib in breast cancer.
Source

Nutrition and cancer (October 2012)

Abstract

Grape polyphenols inhibit akt/mammalian target of rapamycin signaling and potentiate the effects of gefitinib in breast cancer. We recently reported that a combination of dietary grape polyphenols resveratrol, quercetin, and catechin (RQC), at low concentrations, was effective at inhibiting metastatic cancer progression. Herein, we investigate the molecular mechanisms of RQC in breast cancer and explore the potential of RQC as a potentiation agent for the epidermal growth factor receptor (EGFR) therapeutic gefitinib. Our in vitro experiments showed RQC induced apoptosis in gefitinib-resistant breast cancer cells via regulation of a myriad of proapoptotic proteins. Because the Akt/mammalian target of rapamycin (mTOR) signaling pathway is often elevated during development of anti-EGFR therapy resistance, the effect of RQC on the mTOR upstream effector Akt and the negative regulator AMP kinase (AMPK) was investigated. RQC was found to reduce Akt activity, induce the activation of AMPK, and inhibit mTOR signaling in breast cancer cells. Combined RQC and gefitinib decreased gefitinib resistant breast cancer cell viability to a greater extent than RQC or gefitinib alone. Moreover, RQC inhibited Akt and mTOR and activated AMPK even in the presence of gefitinib. Our in vivo experiments showed combined RQC and gefitinib was more effective than the individual treatments at inhibiting mammary tumor growth and metastasis in nude mice. Therefore, RQC treatment inhibits breast cancer progression and may potentiate anti-EGFR therapy by inhibition of Akt/mTOR signaling.