mTOR Flashcards
What is the mechanistic target of rapamycin (mTOR)?
A conserved serine/threonine kinase essential for cell growth, metabolism, and survival.
What are the two distinct mTOR complexes, and what do they regulate?
mTORC1: Regulates cell growth, metabolism, and autophagy.
mTORC2: Controls cytoskeletal organization and cell survival.
What are the key structural domains of mTOR and their functions?
HEAT Domain: Protein-protein interactions.
FAT Domain: Supports complex stability.
FRB Domain: Binds the rapamycin-FKBP12 complex.
Kinase Domain: Catalyzes phosphorylation of target proteins.
What are the main components of mTORC1?
mTOR, Raptor, mLST8, and Deptor.
How is mTORC1 activated and inhibited?
Activated by: Rheb-GTP (stimulated by growth factors and amino acids).
Inhibited by: AMPK under energy stress.
What are the main components of mTORC2?
mTOR, Rictor, Sin1, mLST8, Protor, and Deptor.
How is mTORC2 activated?
Primarily through insulin signaling.
How do amino acids regulate mTORC1 activity?
Activate Rag GTPases, recruiting mTORC1 to the lysosome.
How does AMPK influence mTORC1?
Under low ATP conditions, AMPK inhibits mTORC1 to conserve energy.
What is the role of Rheb GTPase in mTORC1 regulation?
Active Rheb-GTP: Activates mTORC1.
TSC1/TSC2 complex: Acts as a GAP to inactivate Rheb.
What are the key downstream effects of mTORC1?
Activates protein synthesis via S6K and 4E-BP1.
Promotes lipid metabolism through SREBP.
Inhibits autophagy by phosphorylating ULK1.
What are the key downstream effects of mTORC2?
Activates Akt (Ser473) for cell survival signaling.
Modulates cytoskeletal organization via Rho GTPases.
How is mTOR signaling implicated in cancer?
Overactive mTOR promotes cell growth and survival.
Targeted by rapamycin and rapalogs (e.g., everolimus).
What are the potential consequences of mTORC1 dysregulation in metabolic disorders?
Contributes to insulin resistance and obesity.
What are the advantages and challenges of rapamycin as an mTOR inhibitor?
Advantage: Effectively inhibits mTORC1.
Challenges: Limited effects on mTORC2 and long-term metabolic side effects.
