L11 Flashcards
why does 4ebp binding to eif4E decrease trasnalation
because in order for translation to happen, eif4G needs to bind to eif4E
why is eif4A needed for initiation complex
it has RNA helicase activity - gets around structural hinderance like hairpins
what activates eif4A
eif4B
what activates eif4B
S6K
what activates S6K
mTORC1
so what is the S6K pathway
mTORC phosphorylates S6K, which phosphorylates eif4B, which binds eif4A, which allows eif4A to have rna helicase activity
what kind of molecule is S6K
serine threonine kinase
what does he call the 2 main highways of the cell
PI3K and mTORC
what happens to activated RasGTP
interacts with Raf
what are the 3 regions of Raf
CR1, CR2, CR3
CR1 raf
Ras binding domain (N-terminal)
CR2 raf
cysteine rich domain
acts as pseudo substrate
CR3 Raf
Kinase domain
relationship between CR1, CR2, CR3
CR1 and 2 are negative auto-regulatory domains - CR3 is oncogenic if the CR1 and CR2 are deleted
what 4 residues must be activated to activate kinase domain of Raf
SS338, Y341, T491 and S494
why is Raf usually inactive
CR2 binds to kinase domain - so it is folded
how is Raf changed when ras-GDP turns into Ras-GTP
change in conformational structure of Raf such that Ras binding domain preferentially binds Ras gTP
this allows CR2 domain to bind the membrane - and then CR3 kinase domain is opened and active
what does ACTIVE CR3 kinase Raf domain do
phosphorylates MEK
what kinase is responsible for phosphorylating Raf
c-SRC and PKC
when is Raf phosphorylated
once Raf is unfolded (due to Ras-GTP), it moves to membrane and then c-SRC and PKC are at membrane to phosphorylate and activate it
why does Raf go to the membrane
Ras has hydrophobic tail and prenylations - so it will be embedded in the membrane and Bring Raf
what MEK residues does Raf phosphorylate
S218, and S222 of MEK1 and S222 and S2226 of MEK2
difference between MEK1/MEK2
Theyre isoforms – but theyre so similar its called MEK1/MEK2 because theyre functionally very very similar
are MEK1/MEK2 different in vitro or in vivo and why
in vivo because MEK1 has T292 threonine which can be phosphorylated by ERKK
what does MEK1/MEK2 activate
ERK
what does MEK1 stand for
MAP-kianse or ERK-phosphorylateing kinase
what family of kinases is ERK in
MAP kinases
cool thing about MEK1/2
its a dual specificity Kinase meaning it phosphorylates threonine, X, and ten Tyrosine
Thr-X-Tyr
where is Thr-X-Tyr found
activation loop close to 200-202 and 204 on ERK1
near Thr185 and Y187 on ERK2
are ERK1 and ERk2 different in vivo?
yes - Mice can survive without ERK1 but die without ERK2
kinase insert
found on ERK in between kinase domain -
catalytic HRD
found on ERK - histidine, arginine, Aspartic acid
what can ERK phosphorylate
variety of Tis like c-fos, c-jun, elk1, sp1, c-Myc
overall function of ERK
stabilizes Tis like c-myc that promote growth/proliferation
where does ERK phosphorylate c-myc
serine 62 - this stabilizes Mac
GSK3 beta
another kinases that phosphorylates c-MYc at thr58
what are the downstream targets of c-myc
cyclins, kinases like cdk4, p21, p15 (the down regulate proliferation)
does Mac upregulate or down-regulate genes
can do both
other name for ERK
MAPK
other name for MEK
MAPKK
another name for Raf
MAPKKK
