L10 Flashcards
2 molecules that can phosphorylate ser473 on AKT
DNA-dependent protein kinase and mTORC2
what does activated AKT phosphorylate
BAD, FoxO
what happens when BAD is phosphorylated
it is prevented from promoting apoptosis
what kind of molecule is BAD
pro-apoptotic
2 places for BAD phosphorylation
Serine 136 and serine 112
what phosphorylates BAD serine 136
AKT
what phosphorylates BAD serine 112
PIM1, PIM2, PKA
what happens to bad once it is phosphorylated (what does it bind to)
14-3-3 => gets sequestered in cytoplasm and soaks up proteins like a scaffold protein
why is 14-3-3 called that
when they isolated it they used chromatography and gel electrophoresis - it was the numbers of the column and gel
what does BAD do when it’s active (ie. not phosphorylated)
it binds to anti-apoptotic molecule Bcl-XL
BAD displaces Bax, and therefore monomeric BAX will go make a Pore
what happens when Akt phosphorylates FoxO
it prevents FoxO from promoting apoptosis and cell cycle arrest
what does FoxO induce
FasL, and also P27 and P21 - these bind to cdks which inhibit cell cycle proliferation
FasL is a death causing hormone
what does FasL bind
FasR - triggers signalling cascade that promotes apoptosis
what does FoxO bind to once phosphorylated b y Akt
it leaves the nucleus and gets recognized by 14-3-3 => then gets sequestered in cytoplasm
does AKT activate mTORC1
yes but in a long-winded way
first thing AKT phosphorylates in the mTORC1 pathway
it inhibits TSc1 and TSC2 - these are tutor suppressors 0> it does this by phosphorylating TSC2
what does mTOR mean
mammalian target of rapamycin
how do TSC1 and TSC2 affect mTOR
they inhibit mTOR
what kind of molecule is AKT
serine threonine kinase
what is another name for tsc2
tuberin
another name for tsc1
hamartin
how many residues does AKT phosphorylate on TSC2
2 in drosophila, at least 4 in humans
what happens to TSC2 when act phosphorylates it
entire complex becomes unstable and is destroyed
does the tsc complex directly interact with mTOR
no - it interacts with Rheb
