Ras and MAP kinase Flashcards
What are sevenless flies missing?
- no R7, a tyrosine kinase receptor
What does not happen in sevenless flies?
- RTK receptor stimulated by FGF and stimulates production if R7 cell
How was Ras shown in drive cell proliferation?
- 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
What kind of molecule is Ras?
- Small GTPase
How is sos activated?
- 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
How does sos activate ras?
- It is a Ras GEF
- Replaces GDP and Pi on Ras with GTP
- Ras adopts an active conformation and can interact with downstream molecules
Which molecule activates Ras?
sos
Where is Ras anchored?
At the cell membrane
How does GTP binding cause Ras to be activated?
- 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
How does Ras downregulate its own signal?
By hydrolysing GTP
What geographical effect do Ras associated receptors have?
When activated brings proteins to the membrane and recruits cellular proteins into complex
How is Ras regulated?
- inherent GTPase activity
- Ras GDI
How does Ras GDI regulate Ras?
- GDI binds to the lipid anchor of Ras and sequesters it so it unable to embed in the plasma membrane
What kind of molecule is Raf?
Ser/Thr kinase
What is a MAP kinase kinase kinase?
Raf
What is the 1st thing Ras interacts with?
Raf
What is a MAP kinase kinase?
MEK
How is MEK activated?
Serine phosphorylation by Raf
What kind of molecule is MEK?
Thr/tyr kinase
Give an example of a MAP kinase?
ERK
What is the main target of ERK in the Ras pathway?
Class of transcription factors called TCF
What happens once ERK has been phosphorylated?
It can enter the nucleus and phosphorylate transcription factors
What kind of molecule is ERK?
Ser/thr kinase
What happens to the transcription factors once phosphorylated by ERK?
They can bind to the promoters for genes required to enter the cell cycle
What does NF1 do to Ras?
- Acts as a RasGAP
- Inserts arginine finger into GTPase region of Ras
- Increases catalysis by x1000
How can negative feedback of RTK pathways occur?
- 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
