L11 Flashcards

1
Q

why does 4ebp binding to eif4E decrease trasnalation

A

because in order for translation to happen, eif4G needs to bind to eif4E

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2
Q

why is eif4A needed for initiation complex

A

it has RNA helicase activity - gets around structural hinderance like hairpins

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3
Q

what activates eif4A

A

eif4B

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4
Q

what activates eif4B

A

S6K

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5
Q

what activates S6K

A

mTORC1

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6
Q

so what is the S6K pathway

A

mTORC phosphorylates S6K, which phosphorylates eif4B, which binds eif4A, which allows eif4A to have rna helicase activity

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7
Q

what kind of molecule is S6K

A

serine threonine kinase

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8
Q

what does he call the 2 main highways of the cell

A

PI3K and mTORC

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9
Q

what happens to activated RasGTP

A

interacts with Raf

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10
Q

what are the 3 regions of Raf

A

CR1, CR2, CR3

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11
Q

CR1 raf

A

Ras binding domain (N-terminal)

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12
Q

CR2 raf

A

cysteine rich domain

acts as pseudo substrate

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13
Q

CR3 Raf

A

Kinase domain

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14
Q

relationship between CR1, CR2, CR3

A

CR1 and 2 are negative auto-regulatory domains - CR3 is oncogenic if the CR1 and CR2 are deleted

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15
Q

what 4 residues must be activated to activate kinase domain of Raf

A

SS338, Y341, T491 and S494

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16
Q

why is Raf usually inactive

A

CR2 binds to kinase domain - so it is folded

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17
Q

how is Raf changed when ras-GDP turns into Ras-GTP

A

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

18
Q

what does ACTIVE CR3 kinase Raf domain do

A

phosphorylates MEK

19
Q

what kinase is responsible for phosphorylating Raf

A

c-SRC and PKC

20
Q

when is Raf phosphorylated

A

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

21
Q

why does Raf go to the membrane

A

Ras has hydrophobic tail and prenylations - so it will be embedded in the membrane and Bring Raf

22
Q

what MEK residues does Raf phosphorylate

A

S218, and S222 of MEK1 and S222 and S2226 of MEK2

23
Q

difference between MEK1/MEK2

A

Theyre isoforms – but theyre so similar its called MEK1/MEK2 because theyre functionally very very similar

24
Q

are MEK1/MEK2 different in vitro or in vivo and why

A

in vivo because MEK1 has T292 threonine which can be phosphorylated by ERKK

25
Q

what does MEK1/MEK2 activate

A

ERK

26
Q

what does MEK1 stand for

A

MAP-kianse or ERK-phosphorylateing kinase

27
Q

what family of kinases is ERK in

A

MAP kinases

28
Q

cool thing about MEK1/2

A

its a dual specificity Kinase meaning it phosphorylates threonine, X, and ten Tyrosine

Thr-X-Tyr

29
Q

where is Thr-X-Tyr found

A

activation loop close to 200-202 and 204 on ERK1

near Thr185 and Y187 on ERK2

30
Q

are ERK1 and ERk2 different in vivo?

A

yes - Mice can survive without ERK1 but die without ERK2

31
Q

kinase insert

A

found on ERK in between kinase domain -

32
Q

catalytic HRD

A

found on ERK - histidine, arginine, Aspartic acid

33
Q

what can ERK phosphorylate

A

variety of Tis like c-fos, c-jun, elk1, sp1, c-Myc

34
Q

overall function of ERK

A

stabilizes Tis like c-myc that promote growth/proliferation

35
Q

where does ERK phosphorylate c-myc

A

serine 62 - this stabilizes Mac

36
Q

GSK3 beta

A

another kinases that phosphorylates c-MYc at thr58

37
Q

what are the downstream targets of c-myc

A

cyclins, kinases like cdk4, p21, p15 (the down regulate proliferation)

38
Q

does Mac upregulate or down-regulate genes

A

can do both

39
Q

other name for ERK

A

MAPK

40
Q

other name for MEK

A

MAPKK

41
Q

another name for Raf

A

MAPKKK