A possible linkage between AMP‐activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway

Feb 1, 2003Genes to cells : devoted to molecular & cellular mechanisms

A possible connection between energy-sensing and growth-control pathways

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Treatment with AICAR inhibits p70 S6k activities in human corneal epithelial cells.

AMPK activation through AICAR disrupts the phosphorylation of Thr-412 in p70 S6k, essential for its function.
Changes in glucose availability can alter AMPK activity and subsequently influence p70 S6k activity.
Over-expression of mutant AMPK subunits affects p70 S6k activity in specific cell lines.
A variant of p70 S6k resistant to rapamycin is also unresponsive to AICAR, indicating a shared regulatory mechanism.
The findings suggest a possible connection between AMPK and mTOR signaling pathways that regulate energy metabolism.

AI simplified

BACKGROUND: The mammalian target of rapamycin (mTOR) regulates multiple cellular functions including translation in response to nutrients, especially amino acids. AMP-activated protein kinase (AMPK) modulates metabolism in response to energy demand by responding to changes in AMP.

RESULTS: The treatment of SV40-immortalized human corneal epithelial cells (HCE-T cells) with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), widely used as an AMPK activator, inhibits p70 S6k activities. Altered glucose availability, which regulates AMPK activity, also modulates the activity of p70 S6k. AICAR treatment also inhibits phosphorylation of Thr-412 in the p70 S6 kinase (p70 S6k), which is indispensable for the activity. Furthermore, over-expression of mutant AMPK subunits by stable expression in rabbit pulmonary fibroblast cell lines (PS120 cells) also modulates p70 S6k activity. The insensitivity of the rapamycin-resistant p70 S6k variant to AICAR treatment suggests that the inhibition of p70 S6k is mediated through a common effector, supporting a model whereby mTOR and its downstream effector are controlled by AMPK.

CONCLUSION: These results indicate that the AMPK and mTOR signalling pathways are possibly linked. In addition to the mTOR signal acting as a priming switch that modulates p70 S6k activation, AMPK appears to provide an overriding switch linking p70 S6k regulation to cellular energy metabolism.

Full Text

Full text is available at the source.

View full text ↗View full text (PDF) ↗View full text (XML) ↗

A possible linkage between AMP‐activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief