How does AMPK inhibit mTOR?

How does AMPK inhibit mTOR?

Activated AMPK has been shown to inhibit mTORC1 signaling by two mechanisms: phosphorylation of TSC2 at Ser-1387, which diminishes contact of mTORC1 with an obligatory activator Rheb-GTP (19), and the inhibitory phosphorylation of the mTORC1 subunit Raptor at Ser-792 (26).

Does AMPK phosphorylate mTOR?

Many details of the molecular mechanism by which AMPK inhibits mTORC1 signaling have also been decoded in the past 5 years. AMPK directly phosphorylates at least two proteins to induce rapid suppression of mTORC1 activity, the TSC2 tumor suppressor and the critical mTORC1 binding subunit raptor.

What is the role of AMPK and mTOR?

Mammalian target of rapamycin (mTOR),is one of the downstream targets of AMPK functions as an intracellular nutrient sensor to control protein synthesis, cell growth, and metabolism.

What is the difference between mTOR and AMPK?

Interestingly, like AMPK, the mTOR serine/threonine kinase plays key roles not only in growth control and cell proliferation but also in metabolism. These findings have broad implications for the control of cell growth by nutrients in a number of cellular and organismal contexts.

How is mTOR activated?

Signaling through mammalian target of rapamycin (mTOR) is activated by amino acids, insulin, and growth factors, and impaired by nutrient or energy deficiency. mTOR regulates numerous components involved in protein synthesis, including initiation and elongation factors, and the biogenesis of ribosomes themselves.

How does mTOR inhibit autophagy?

mTORC1 tightly regulates autophagy by suppressing autophagy induction via phosphorylation-dependent inhibition of ULK1/2 and the VPS34 complex and by preventing global expression of lysosomal and autophagy genes through TFEB phosphorylation.

What inhibits mTOR?

Rapamycin is the main mTOR inhibitor, but deforolimus (AP23573), everolimus (RAD001), and temsirolimus (CCI-779), are the newly developed rapamycin analogs.

What happens if the mTOR pathway is inhibited?

The inhibition of mTOR blocks the binding of the accessory protein raptor (regulatory-associated protein of mTOR) to mTOR, but that is necessary for downstream phosphorylation of S6K1 and 4EBP1. As a consequence, S6K1 dephosphorylates, which reduces protein synthesis and decreases cell mortality and size.

Does mTOR induce autophagy?

mTOR promotes anabolic metabolism and inhibits autophagy induction. Therefore, the regulation of autophagy with mTOR inhibitors provides a new therapeutic strategy for a variety of diseases, including neurodegenerative diseases, diabetes, and cancer.

How many mTOR inhibitors are there?

At present, mTOR inhibitors are divided into four categories: Antibiotic allosteric mTOR inhibitors (first generation), ATP-competitive mTOR inhibitors (second generation), mTOR/PI3K dual inhibitors (second generation) and other new mTOR inhibitors (third generation).