10 Flashcards
Compare Raptor and Rictor in the mTOR pathway?
Raptor defines mTORC1, which regulates cell growth.
Rictor defines mTORC2, which controls AKT signaling, survival/proliferation (autophagy or survival)
Normally, TSC1/2 act like what?
GAP’s
what happens when/if Rheb is KO?
Rheb KO results in a catabolic, energy-conserving state with increased autophagy and reduced anabolic processes.
(no-little growth/survival)
what is S6K1 in the mTOR pathway?
S6K1 is a downstream effector of mTORC1 that promotes protein synthesis and cell growth.
Its inhibition (due to low mTORC1 activity) leads to autophagy activation by reducing translation and allowing ULK1 activation.
what kind or proteins are Raptor and Rictor?
Scaffolding proteins that regulate mTOR’s kinase activity
what is essential for AKT activation?
PDK1 & mTORC2: Essential for AKT activation by providing key phosphorylation events.
If Smo is activated Gli is……
If Smo (Smoothened) is activated, Gli is activated
(acts as a transcriptional activator) in the Hedgehog signaling pathway.
mTOR Crosstalk with Hedgehog Signaling
Active mTORC1 promotes Gli1 translation via S6K1, increasing Hh target gene expression.
Growth factors and nutrients that activate mTORC1 can amplify Gli-driven transcription.
Nutrient Rich Environment (AMPK, mTORC1, ULK1)
AMPK: Down
mTORC1: Up (Survival)
ULK1: Down
Nutirent Poor Environment (AMPK, mTORC1, ULK1)
AMPK: Up
mTORC1: Down (autophagy)
ULK1: Up
what is ULK1?
ULK1 (Unc-51 Like Autophagy Activating Kinase 1)
is a key kinase that initiates autophagy by forming a complex with other proteins to promote autophagosome formation.
AMPK and ULK1 relationship ?
AMPK activates (phos’n) ULK1 under low energy conditions, promoting autophagy as a survival response.
