Ras and MAP kinase Flashcards

1
Q

What are sevenless flies missing?

A
  • no R7, a tyrosine kinase receptor
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2
Q

What does not happen in sevenless flies?

A
  • RTK receptor stimulated by FGF and stimulates production if R7 cell
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3
Q

How was Ras shown in drive cell proliferation?

A
  • Temperature sensitive sevenless flies were grown at a non-permissive temperature
  • If mutant alleles of Ras were expressed by flies even at non-permissive temperature the flies could still develop R7 cell
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4
Q

What kind of molecule is Ras?

A
  • Small GTPase
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5
Q

How is sos activated?

A
  • RTK activated and phosphorylates itself
  • Recruits Grb2 adaptor with SH2 domain to bind to phosphotyrosine residue
  • Also contains SH3 domains which bind to polyproline sequences on sos
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6
Q

How does sos activate ras?

A
  • It is a Ras GEF
  • Replaces GDP and Pi on Ras with GTP
  • Ras adopts an active conformation and can interact with downstream molecules
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7
Q

Which molecule activates Ras?

A

sos

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8
Q

Where is Ras anchored?

A

At the cell membrane

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9
Q

How does GTP binding cause Ras to be activated?

A
  • GTP binding causes conformational change which exposes switch I and switch II regions
  • These switch regions can interact with (and in many cases activate) downstream effector molecules
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10
Q

How does Ras downregulate its own signal?

A

By hydrolysing GTP

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11
Q

What geographical effect do Ras associated receptors have?

A

When activated brings proteins to the membrane and recruits cellular proteins into complex

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12
Q

How is Ras regulated?

A
  • inherent GTPase activity
  • Ras GDI
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13
Q

How does Ras GDI regulate Ras?

A
  • GDI binds to the lipid anchor of Ras and sequesters it so it unable to embed in the plasma membrane
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14
Q

What kind of molecule is Raf?

A

Ser/Thr kinase

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15
Q

What is a MAP kinase kinase kinase?

A

Raf

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16
Q

What is the 1st thing Ras interacts with?

A

Raf

17
Q

What is a MAP kinase kinase?

A

MEK

18
Q

How is MEK activated?

A

Serine phosphorylation by Raf

19
Q

What kind of molecule is MEK?

A

Thr/tyr kinase

20
Q

Give an example of a MAP kinase?

A

ERK

21
Q

What is the main target of ERK in the Ras pathway?

A

Class of transcription factors called TCF

22
Q

What happens once ERK has been phosphorylated?

A

It can enter the nucleus and phosphorylate transcription factors

23
Q

What kind of molecule is ERK?

A

Ser/thr kinase

24
Q

What happens to the transcription factors once phosphorylated by ERK?

A

They can bind to the promoters for genes required to enter the cell cycle

25
Q

What does NF1 do to Ras?

A
  • Acts as a RasGAP
  • Inserts arginine finger into GTPase region of Ras
  • Increases catalysis by x1000
26
Q

How can negative feedback of RTK pathways occur?

A
  • Some substrates are in the form of negative feedback targets
  • Can phosphorylate RTKS and downregulate them or phosphorylate sos and prevent its association with Grb2